Electrical stimulation system and method for stimulating tissue in the brain to treat a neurological condition

ABSTRACT

According to one aspect, a stimulation system is provided for electrically stimulating a predetermined site to treat a neurological condition. The system includes an electrical stimulation lead adapted for implantation in communication with a predetermined site, wherein the site is brain tissue site. The stimulation lead includes one or more stimulation electrodes adapted to be positioned in the predetermined site. The system also includes a stimulation source that generates the stimulation pulses for transmission to the one or more stimulation electrodes of the stimulation lead to deliver the stimulation pulses to the predetermined site to treat a neurological disorder or condition.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/503,627, filed Jul. 15, 2009, now U.S. Pat. No. 8,364,271, which is acontinuation of U.S. application Ser. No. 11/078,114, filed Mar. 11,2005, now abandoned, which claims the benefit of U.S. ProvisionalApplication No. 60/552,674, filed Mar. 11, 2004, the disclosures ofwhich are fully incorporated herein by reference for all purposes.

TECHNICAL FIELD

This invention relates generally to electrical stimulation of a person'sbrain and in particular to an electrical stimulation system and methodfor stimulating tissue in the brain to treat a neurological condition,for example pain.

BACKGROUND OF THE INVENTION

Many people experience adverse conditions associated with functions ofthe cortex, the thalamus, and other brain structures. Such conditionshave been treated effectively by delivering electrical energy to one ormore target areas of the brain. One method of delivering electricalenergy to the brain involves inserting an electrical stimulation leadthrough a burr hole formed in the skull and then positioning the lead ina precise location proximate a target area of the brain to be stimulatedsuch that stimulation of the target area causes a desired clinicaleffect. For example, one desired clinical effect may be cessation oftremor from a movement disorder such as Parkinson's Disease. A varietyof other clinical conditions may also be treated with deep brainstimulation, such as essential tremor, tremor from multiple sclerosis orbrain injury, or dystonia or other movement disorders. The electricalstimulation lead implanted in the brain is connected to an electricalsignal generator implanted at a separate site in the body, such as inthe upper chest.

Chronic pain afflicts approximately 86 million Americans and it isestimated that United States business and industry loses about $90billion dollars annually to sick time, reduced productivity, and directmedical and other benefit costs due to chronic pain among employees.Because of the staggering number of people affected by chronic pain, anumber of therapies have been developed that attempt to alleviate thesymptoms of this condition. Such therapies include narcotics,non-narcotics, analgesics, antidepressants, anticonvulsants, physicaltherapy, biofeedback, transcutaneous electrical nerve stimulation(TENS), as well as less conventional or alternative therapies. Othertreatment options involve neuroaugmentive techniques such as spinal cordstimulation or intrathecal pumps. For a subset of patients, however,these therapies are inefficacious and more invasive procedures such asblocks, neurolysis and ablative procedures become the only options fortreatment. In particular, ablative procedures, although infrequentlyutilized, are the primary alternative for patients unresponsive to othermodes of treatment. Such procedures, however, have the fundamentallimitation of being inherently irreversible and being essentially a“one-shot” procedure with little chance of alleviating or preventingpotential side effects. In addition, there is a limited possibility toprovide continuous benefits as the pathophysiology underlying thechronic pain progresses and the patient's symptoms evolve. Because ofthe inherent disadvantages of ablative procedures, electricalstimulation of the brain has become an attractive neurosurgicalalternative to alleviate the symptoms of chronic pain.

Electrical stimulation of the brain for chronic pain has been used sincethe 1950s when temporary electrodes were implanted in the septal regionfor psychosurgery in patients with schizophrenia and metastaticcarcinoma. In particular, electrodes were placed in the septumpellucidum in a region anterior and inferior to the foramen of Monro. Inthe 1960s, there were reports of stimulation of both the caudate nucleusand the septal region in six patients with intractable pain, butsuccessful pain relief was obtained in only one patient. Despite theseearlier reports of septal and caudate stimulation, current applicationsof electrical stimulation for pain involve thalamic, medial lemniscus,internal capsule stimulation, periventricular gray and pariaqueductalgray stimulation. For example, thalamic stimulation for pain relief wasfirst reported for stimulation along the ventroposterolateral nucleusand ventralis posterior to relieve chronic intractable deafferentationpain and stimulation along the ventroposteromedial nucleus to relieverefractory facial pain. With respect to internal capsule stimulation,chronic stimulating electrodes have been implanted in the posterior limbof the internal capsule in a number of patients, including patients withlower-extremity pain and spasticity following spinal cord injury.

Although the above-mentioned target sites are all deep brain stimulationtarget sites, several studies have supported the role of motor cortexstimulation for pain control. For example, in the process of performingsensory cortex stimulation in an attempt to relieve thalamic pain, itwas found that stimulation of the precentral gyrus/motor cortex waseffective in relieving thalamic pain. Interestingly, stimulation of thesensory cortex exacerbated the pain in many patients.

Therefore, despite previous attempts to alleviate the symptoms ofchronic pain by deep brain or cortical stimulation, there is still anunmet need for a method of treating chronic pain that is effective in alarger subset of the patient population.

BRIEF SUMMARY OF THE INVENTION

The electrical stimulation system and method of the present inventionmay reduce or eliminate certain problems and disadvantages associatedwith previous techniques for treating neurological conditions, such aspain, for example.

According to one embodiment, an electrical stimulation system isprovided for electrically stimulating target tissue in a person's brainto treat a neurological condition. The system includes an electrodeadapted for implantation into a person's skull for electricalstimulation of target tissue in the person's brain. The system alsoincludes a pulse generating source operable to generate electricalstimulation pulses for transmission to the electrodes to deliver theelectrical stimulation pulses to the target tissue in the brain toadjust the level of activity in the target tissue in the brain to treatthe neurological condition.

The target tissue can be a cortical tissue site, for example thesomatosensory cortex or sensory cortex. The smoatosensory cortexincludes, but is not limited to the primary somatosensory cortex, thesecondary somatosensory cortex, and the somatosensory associationcomplex. Yet further, the target tissue can be identified by mapping theperson's brain. Mapping a person's or subject's brain providesinformation to identify areas of the brain that exhibit altered neuronalactivity, such as increased or decreased neuronal activity. Areas ofaltered neuronal activity can therefore be identified as target sitesfor stimulation. Still further, a target site for stimulation can alsoinclude areas identified in the cortex are undergoing or have undergonereorganization.

Additional target sites also include, but are not limited to thecerebellum, which can also be activated in sensory stimulation. Thus,other targets can also include any region of the brain associated or incommunication with the sensory cortex, which includes any region orstructure, as well as any connections to and from the sensory cortex.Association with the sensory cortex includes the functional areas of thesensory cortex for example, but not limited to the primary somatosensorycortex, the secondary somatosensory cortex, the somatosensoryassociation complex, primary visual cortex, secondary and tertiaryvisual cortices, visual association cortex, primary auditory cortex,auditory association cortex, gustatory cortex, and vestibular cortex,other brain regions that receive somatic inputs, for example, theposterior parietal lobe, as well as any brain region that is stimulatedby sensory stimulation, such as the cerebellum. Thus, stimulation of thesensory cortex includes the somatosensory processing cortical regions ofthe brain and sub-cortical regions or structures, as well as the anybrain region in which there are projection connections for example, thebasal ganglia, the striatum, the motor cortex, supplementary motorcortex or area, the posterior parietal cortex, the thalamus (e.g., theventral posterior nucleus of the thalamus), brainstem, periaqueductalgrey, dorsal column nuclei, and the spinal cord (e.g., dorsal horn ofthe spinal cord).

Accordingly, the present invention relates to modulation of neuronalactivity to affect neurological, neuropsychological or neuropsychiatricactivity. The present invention finds particular application in themodulation of neuronal function or processing to affect a functionaloutcome. The modulation of neuronal function is particularly useful withregard to the prevention, treatment, or amelioration of neurological,psychiatric, psychological, conscious state, behavioral, mood, andthought activity (unless otherwise indicated these will be collectivelyreferred to herein as “neurological activity” which includes“psychological activity” or “psychiatric activity”). When referring to apathological or undesirable condition associated with the activity,reference may be made to a neurological disorder which includes“psychiatric disorder” or “psychological disorder” instead ofneurological activity or psychiatric or psychological activity. Althoughthe activity to be modulated usually manifests itself in the form of adisorder such as a attention or cognitive disorders (e.g., AutisticSpectrum Disorders); mood disorder (e.g., major depressive disorder,bipolar disorder, and dysthymic disorder) or an anxiety disorder (e.g.,panic disorder, posttraumatic stress disorder, obsessive-compulsivedisorder and phobic disorder); neurodegenerative diseases (e.g.,multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis(ALS), Parkinson's disease, Huntington's Disease, Guillain-Barresyndrome, myasthenia gravis, and chronic idiopathic demyelinatingdisease (CID)), movement disorders (e.g., dyskinesia, tremor, dystonia,chorea and ballism, tic syndromes, Tourette's Syndrome, myoclonus,drug-induced movement disorders, Wilson's Disease, ParoxysmalDyskinesias, Stiff Man Syndrome and Akinetic-Ridgid Syndromes andParkinsonism), epilepsy, tinnitus, pain, phantom pain, diabetesneuropathy, one skilled in the art appreciates that the invention mayalso find application in conjunction with enhancing or diminishing anyneurological or psychiatric function, not just an abnormality ordisorder. Neurological activity that may be modulated can include, butnot be limited to, normal functions such as alertness, conscious state,drive, fear, anger, anxiety, repetitive behavior, impulses, urges,obsessions, euphoria, sadness, and the fight or flight response, as wellas instability, vertigo, dizziness, fatigue, fotofobia, fonofobia,concentration dysfunction, memory disorders, symptoms of traumatic braininjury (whether physical, emotional, social or chemical), autonomicfunctions, which includes sympathetic and/or parasympathetic functions(e.g., control of heart rate), somatic functions, and/or entericfunctions.

Particular embodiments of the present invention may provide one or moretechnical advantages. According to the present invention, an electricalstimulation system is used to provide therapeutic electrical stimulationto target tissue in a person's brain to treat a neurological condition.In particular, brain mapping or brain imaging information and/orneurophysiological information (e.g., evoked potentials, inducedpotentials, EEG, MEG) can be used to identify target tissue in aperson's brain having a notable level of activity associated with aneurological condition, such as pain or tinnitus, for example. Suchtechniques to map the brain include, but are not limited to positronemission tomography (PET), magnetic resonance imaging (MRI), functionalMRI (fMRI), electroencephalography (EEG), magnetoencephalography (MEG),x-ray computed tomography (CT), single photon emission computedtomography (SPECT), brain electrical activity mapping (BEAM),transcranial magnetic stimulation (TMS), electrical impedance tomography(EIT), near-infrared spectroscopy (NIRS) and optical imaging.

The brain mapping information may include imaging information obtainedby imaging at least a portion of the person's brain using one or moreimaging techniques. Instead or in addition, the brain imaginginformation may include imaging information obtained from imaging of thebrains of one or more other patients who experience the same or similarcondition as the person. In certain embodiments, an electrode or anelectrical stimulation lead having a number of electrodes is implantedinside a person's skull such that one or more of the electrodes arelocated in communication with the identified target tissue in the brain.The electrodes deliver electrical stimulation pulses to the identifiedtarget tissue, which partially or completely alleviates the condition inthe person's body, which may significantly increase the person's qualityof life. The electrode or electrical stimulation lead may be preciselypositioned using a neuronavigation system that includes brain imaginginformation and mapping data obtained from the imaging of the person'sbrain or from the imaging of the brains of one or more other patients.In addition, non-invasive transcranial magnetic stimulation (TMS) of thetarget tissue may be performed before surgically implanting theelectrical stimulation lead in order to determine whether the person isa candidate for receiving an implanted electrical stimulation system.

In certain embodiments, the electrical stimulation system may also beable to provide electrical stimulation of the same or different targettissue in the brain to reduce, enhance, or otherwise treatneuroplasticity effects that may be associated with the electricalstimulation of the target tissue for treating the neurologicalcondition. As a result, in certain embodiments, the efficacy periodassociated with a particular set of stimulation parameters may beextended. This may help prevent the additional time and expenseassociated with one or more return visits to the treating physician fordetermining and entering new sets of efficacious parameters. Especiallywhere the treatment is to continue over a relatively long period oftime, such as a number of months or years, avoiding this additional timeand expense may provide a significant advantage. As another example, inother situations, the further development of neuroplasticity effectsalready in existence due to injury or disease may be prevented, delayed,or otherwise reduced, or such pre-existing neuroplasticity effects maybe reversed in whole or in part. As a result, in certain embodiments,undesirable conditions resulting from such pre-existing neuroplasticityeffects may be prevented from progressing further, may be reduced, ormay even be eliminated. In certain other embodiments, such as where theperson has experienced a stroke, for example, the electrical stimulationsystem may provide electrical stimulation of the same or differenttarget tissue in the brain to enhance or promote neuroplasticityeffects.

The foregoing has outlined rather broadly the features and technicaladvantages of the present invention in order that the detaileddescription of the invention that follows may be better understood.Additional features and advantages of the invention will be describedhereinafter which form the subject of the claims of the invention. Itshould be appreciated by those skilled in the art that the conceptionand specific embodiment disclosed may be readily utilized as a basis formodifying or designing other structures for carrying out the samepurposes of the present invention. It should also be realized by thoseskilled in the art that such equivalent constructions do not depart fromthe spirit and scope of the invention as set forth in the appendedclaims. The novel features which are believed to be characteristic ofthe invention, both as to its organization and method of operation,together with further objects and advantages will be better understoodfrom the following description when considered in connection with theaccompanying figures. It is to be expressly understood, however, thateach of the figures is provided for the purpose of illustration anddescription only and is not intended as a definition of the limits ofthe present invention.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

For a more complete understanding of the present invention, reference isnow made to the following descriptions taken in conjunction with theaccompanying drawing, in which:

FIGS. 1A-1B illustrate example electrical stimulation systems forelectrically stimulating target nerve tissue in the brain identifiedthrough imaging of the brain to treat a condition in the body and, incertain embodiments, provide reduced or enhanced neuroplasticity effectsin the brain;

FIGS. 2A-2I illustrate example electrical stimulation leads that may beused to electrically stimulate target nerve tissue in the brainidentified through imaging of the brain to treat a condition in the bodyand, in certain embodiments, provide reduced or enhanced neuroplasticityeffects in the brain;

FIG. 3 illustrates example placement of the electrical stimulationsystem shown in FIGS. 1A-1B within a person's body;

FIG. 4 is a cross-section of a portion of the person's head shown inFIG. 3, illustrating an example location of the electrical stimulationlead;

FIG. 5 illustrates an example method for determining an optimal locationand implanting the stimulation system of FIGS. 1A-1B into a person inorder to electrically stimulate target nerve tissue in the brainidentified through imaging of the brain to treat a condition in thebody;

FIG. 6 illustrates an example stimulation set;

FIG. 7 illustrates a number of example stimulation programs, each ofwhich includes a number of stimulation sets; and

FIG. 8 illustrates example execution of a sequence of stimulation setswithin an example stimulation program.

FIG. 9A and FIG. 9B illustrate fMRI activity (thresholded at T>7)overlayed on saggital, transverse and coronal slices (FIG. 9A) as wellas a surface reconstruction of the patient's brain (FIG. 9B). Arrowindicates area of V1 pain sensation, located within the left postcentralgyrus. Other areas of activity were found in left primary sensorymotorcortex, supplementary motor area, right cerebellum and are related tothe motor activity of the left hand and arm rubbing the right V1 skinarea.

FIG. 10 shows that the amount of pain suppression is related to thestimulation frequency used. The same relation is seen for the timerequired for the phantom eye to disappear.

FIGS. 11A-11C show site of stimulation. FIG. 11A shows a postoperativeX-ray demonstrating the position of the lead. FIG. 11B showspostoperative CT comparison to preoperative fMRI (FIG. 11C). Comparingthe anatomy of the preoperative fMRI with the postoperative CT scandemonstrates the lead is positioned over the somatosensory cortex. Thearea of the V1 pain sensation is located more caudally (FIG. 9) andcannot be seen on these images.

DETAILED DESCRIPTION

It is readily apparent to one skilled in the art that variousembodiments and modifications can be made to the invention disclosed inthis application without departing from the scope and spirit of theinvention.

I. Definitions

As used herein, the use of the word “a” or “an” when used in conjunctionwith the term “comprising” in the claims and/or the specification maymean “one,” but it is also consistent with the meaning of “one or more,”“at least one,” and “one or more than one.” Still further, the terms“having,” “including,” “containing” and “comprising” are interchangeableand one of skill in the art is cognizant that these terms are open endedterms.

As used herein, the term “affective disorders” refers to a group ofdisorders that are commonly associated with co-morbidity of depressionand anxiety symptoms.

As used herein, the term “chronic pain” can generally be characterizedas being nociceptive or non-nociceptive including neuropathic pain. Yetfurther, it can also be characterized as pain that has lasted for aperiod of time, for example, more than three months. Chronic paingenerally also has significant psychological and emotional affects andcan limit a person's ability to fully function.

As used herein, the term “acute pain” refers to more a recent onset ofpain, pain associated with an injury or trauma or immediate paintriggered by injury. Acute pain can also be referred to as “phasic.”Generally, acute pain is associated with a greater intensity of painand/or an impairment in functionality for the person.

As used herein, the term “sub-acute pain” refers to slow, insidiousonset of pain, which can also be characterized as dull and achy. Attimes, sub-acute pain can not be easily localized, however, it may bepossible to localize the pain depending upon the condition. Typically,sub-acute pain creates a discomfort for the person, but does nottypically impair functionality for the person.

As used herein, the term “dementia” refers to the loss, of cognitive andintellectual functions without impairment of perception orconsciousness. Dementia is typically characterized by disorientation,impaired memory, judgment, and intellect, and a shallow labile affect.

As used herein, the term “deafferentation” refers to a loss of thesensory input from a portion of the body.

As used herein, the term “in communication” refers to the stimulationlead being adjacent, in the general vicinity, in close proximity, ordirectly next to or directly on the predetermined stimulation site, forexample an area of the cortex, or an area associated with the sensorycortex, or any subcortical area or structure that is projections to orfrom the sensory cortex, or any identified brain region or areadetermined by mapping the brain of a subject suffering from aneurological condition. Thus, one of skill in the art understands thatthe lead or electrode is “in communication” with the target tissue orsite if the stimulation results in a modulation of neuronal activityresulting in the desired response, such as modulation of theneurological disorder.

The terms “mammal,” “mammalian organism,” “subject,” or “patient” or“person” are used interchangeably herein and include, but are notlimited to, humans, dogs, cats, horses and cows. The preferred patientsare humans.

As used herein the term “modulate” refers to the ability to regulatepositively or negatively neuronal activity. Thus, the term modulate canbe used to refer to an increase, decrease, masking, altering, overridingor restoring of neuronal activity.

As used herein, the term “neurology” or “neurological” refers toconditions, disorders, and/or diseases that are associated with thenervous system. The nervous system comprises two components, the centralnervous system, which is composed of the brain and the spinal cord, andthe peripheral nervous system, which is composed of ganglia and theperipheral nerves that lie outside the brain and the spinal cord. One ofskill in the art realizes that the nervous system may be separatedanatomically, but functionally they are interconnected and interactive.Yet further, the peripheral nervous system is divided into the autonomicsystem (parasympathetic and sympathetic), the somatic system and theenteric system. Thus, any condition, disorder and/or disease thateffects any component or aspect of the nervous system (either central orperipheral) is referred to as a neurological condition, disorder and/ordisease. As used herein, the term “neurological” or “neurology”encompasses the terms “neuropsychiatric” or “neuropsychiatry” and“neuropsychological” or “neuropsychological”. Thus, a neurologicaldisease, condition, or disorder includes, but is not limited tocognitive disorders, affective disorders, movement disorders, mentaldisorders, pain disorders, sleep disorders, etc. For non-inclusiveexamples, neurological disorders include pain, chronic pain, tinnitus,stroke, hypertension, migraine headaches, depression, and epilepsy.

As used herein, the term “neuropsychiatry” or “neuropsychiatric” refersto conditions, disorders and/or diseases that relate to both organic andpsychic disorders of the nervous system.

As used herein, the term “neuropsychological” or “neuropsychologic”refers to conditions, disorders and/or disease that relate to thefunctioning of the brain and the cognitive processors or behavior.

As used herein, the term “neuronal” or “nervous” refers to a neuronwhich is a morphologic and functional unit of the brain, spinal column,and peripheral nerves.

As used herein, the term “nociceptive pain” involves direct activationof the nociceptors, such as mechanical, chemical, and thermal receptors,found in various tissues, such as bone, muscle, vessels, viscera, andcutaneous and connective tissue. Nociceptive pain can also be referredto as somatic pain. The afferent somatosensory pathways are thought tobe intact in nociceptive pain and examples of such pain include cancerpain from bone or tissue invasion, non-cancer pain secondary todegenerative bone and joint disease or osteoarthritis, and failed backsurgery.

As used herein, the term “non-nociceptive pain” occurs in the absence ofactivation of peripheral nociceptors. Non-nociceptive pain can also bereferred to as neuropathic pain, or deafferentation pain.Non-nociceptive pain often results from injury or dysfunction of thecentral or peripheral nervous system. Such damage may occur anywherealong the neuroaxis and includes thalamic injury or syndromes (alsoreferred to as central pain, supraspinal central pain, or post-strokepain); stroke; traumatic or iatrogenic trigeminal (trigeminalneuropathic) brain or spinal cord injuries; phantom limb or stump pain;postherpetic neuralgia; anesthesia dolorosa; brachial plexus avulsion;complex regional pain syndrome I and II; postcordotomy dysesthesia; andvarious peripheral neuropathies, inclusive of pain associated with orrelated to vascular pathology (vasculitis, angina pectoris, etc.) bothperipheral vascular pathology, central or cerebral vascular pathology,and/or cardiac vascular abnormalities.

The term “pain” as used herein refers to an unpleasant sensation oraltered sensory perception. For example, the subject experiencesdiscomfort, distress or suffering. Pain of a moderate or high intensityis typically accompanied by anxiety. Thus, one of skill in the art iscognizant that pain may have dual properties, for example sensation andemotion. Examples of pain or altered sensory perception can include, butare not limited to paresthesias, dysesthesias, synesthesia,hyperalgesia, allodynia, phantom perceptions, pressure feeling, as wellas motor system activities depending on sensory input (e.g., Parkinsons,myoclonias, dystonias, tremor, stiff man syndrome, dyskinesia, tremor,dystonia, chorea and ballism, tic syndromes, Tourette's Syndrome,myoclonus, drug-induced movement disorders, Wilson's Disease, ParoxysmalDyskinesias, Stiff Man Syndrome and Akinetic-Ridgid Syndromes andParkinsonism, etc.). Pain can include chronic pain, acute pain orsubacute pain.

As used herein, the term “somatosensory system” refers to the peripheralnervous system division comprising primarily afferent somatic sensoryneurons and afferent visceral sensory neurons that receive sensoryinformation from skin and deep tissue, including the 12 cranial and 21spinal nerves.

As used herein, the term “somatosensory cortex” or “sensory cortex”includes the primary somatosensory cortex, secondary somatosensorycortex and the somatosensory association cortex, as well as the Brodmannareas associated therewith. Still further, the sensory cortex includesall cortical sites having projections to or from the sensory cortex, aswell as the subcortical sites having projections to or from the sensorycortex.

As used herein, the term “primary somatosensory cortex” refers to thebrain region located in the postcentral gyrus and in the posterior partof the paracentral lobule. The primary somatosensory cortex alsoincludes Brodmann areas 3, 1 and 2.

As used herein, the term “secondary somatosensory cortex” refers to thebrain region that lies ventral to the primary somatosensory area alongthe superior bank of the lateral sulcus.

As used herein, the term “somatosensory association cortex” refers tothe brain areas of the superior parietal lobule, and supramarginalgyrus. The somatosensory association cortex also includes Brodmann areas5, 7, and 40.

As used herein, the term “stimulate” or “stimulation” refers toelectrical, chemical, magnetic, heat/cold and/or ultrasonic stimulationthat modulates the predetermined sites in the brain.

As used herein, the term “treating” and “treatment” refers tostimulating a peripheral nervous tissue site so that the subject has animprovement in the disease, for example, beneficial or desired clinicalresults. For purposes of this invention, beneficial or desired clinicalresults include, but are not limited to, alleviation of symptoms,alleviation of pain, diminishment of extent of disease, stabilized(i.e., not worsening) state of disease, delay or slowing of diseaseprogression, amelioration or palliation of the disease state, andremission (whether partial or total), whether detectable orundetectable. One of skill in the art realizes that a treatment mayimprove the disease condition, but may not be a complete cure for thedisease.

As used herein, the term “proximate” means on, in, adjacent, or near.Thus, one or more of the electrodes on an electrical stimulation leadare adapted to be positioned on, in, adjacent, or near the identifiedtarget tissue in the brain.

As used herein, the term “tissue in the brain” includes any tissue inany associated with the brain, including gray matter and white matterthat make up the brain.

II. Electrical Stimulation System

According to the present invention, an electrical stimulation system isused to electrically stimulate target tissue in a person's brain totreat a neurological condition. The target tissue can be in a corticalregion of the brain, for example, the somatosensory cortex, whichincludes the primary, the secondary somatosensory cortex, and thesomatosensory association complex. Still further, the somatosensorycortex also includes Brodmann areas 1, 2, 3, 5, and 7. The somatosensorycortex, in certain embodiments, is stimulated either directly orindirectly to treat pain.

Yet further, an another embodiment of the present invention comprises,at least a portion of a person's brain is imaged using one or moreimaging techniques to identify target tissue in the brain having anotable level of activity, such as overactivity or underactivity, forexample, associated with a condition, such as pain or tinnitus. Anelectrical stimulation lead having a number of electrodes is implantedinside a person's skull such that one or more of the electrodes arelocated in communication with the identified target tissue in the brain.

The electrodes deliver electrical stimulation pulses to the identifiedtarget brain tissue to adjust the level of activity in the identifiedtarget nerve tissue in the brain to treat the neurological condition.For example, if the identified target tissue in the brain is overactive,the one or more electrodes may deliver appropriate electricalstimulation pulses to decrease the activity of the identified targettissue to treat the condition. Similarly, if the identified targettissue in the brain is underactive, the one or more electrodes maydeliver appropriate electrical stimulation pulses to increase theactivity of the identified target tissue to treat the neurologicalcondition.

The neurological condition may be any condition associated with anotable level of activity, such as overactivity or underactivity forexample, in the identified target tissue in the person's brain. Exampleconditions may include pain in a region of the person's body, tinnitus,depression, and other neurological disorders. In some instances, thenotable level of activity in the identified target tissue in theperson's brain, and thus the condition in the person's body, is causedby damaged, altered or otherwise abnormally functioning nerve tissue inthe person's body correlating to the identified target tissue in theperson's brain. For example, with respect to pain, damaged, altered orotherwise abnormally functioning nerve tissue in a region of a person'sbody that causes pain in that region or another region of the person'sbody may cause overactivity or underactivity in tissue in the person'sbrain that correlates to the abnormally functioning nerve tissue. Asanother example, with respect to tinnitus, damaged, altered or otherwiseabnormally functioning nerve tissue in a person's auditory system orbrain that causes tinnitus may cause overactivity or underactivity innerve tissue in the person's brain that correlates to the abnormallyfunctioning nerve tissue.

FIGS. 1A-1B illustrate example electrical stimulation systems 10 forelectrically stimulating target tissue in the brain identified throughimaging of the brain to treat a condition in the body and, in certainembodiments, to provide reduced or enhanced neuroplasticity effects inthe brain. Stimulation system 10 generates and applies a stimulus totarget tissue in a person's brain, for example, the somatosensorycortex. In certain embodiments, the target tissue is identified throughimaging of the person's brain as having a notable level of activity toadjust the level of activity in the identified target tissue to treat aneurological condition.

In general terms, stimulation system 10 includes an implantableelectrical stimulation source 12 and an implantable electricalstimulation lead 14 for applying the stimulation signal to thepredetermined site or target tissue site. In operation, both of theseprimary components are implanted in the person's body. In certainembodiments, stimulation source 12 is coupled directly to a connectingportion 16 of electrical stimulation lead 14. In certain otherembodiments, stimulation source 12 is not coupled directly tostimulation lead 14 and stimulation source 12 instead communicates withstimulation lead 14 via a wireless link. For example, such a stimulationsystem 10 are described in the following U.S. Pat. Nos. 6,748,276;5,938,690, each of which is incorporated by reference in its entirety.In certain other embodiments, stimulation source 12 and electrodes 18are contained in an “all-in-one” microstimulator or other unit, such asa Bion® microstimulator manufactured by Advanced Bionics Corporation. Inany case, stimulation source 12 controls the electrical stimulationpulses transmitted to electrodes 18 (which may be located on astimulating portion 20 of an electrical stimulation lead 14), implantedin communication with the target tissue, according to appropriatestimulation parameters (e.g., duration, amplitude or intensity,frequency, etc.). A doctor, the patient, or another user of stimulationsource 12 may directly or indirectly input or modify stimulationparameters to specify or modify the nature of the electrical stimulationprovided.

In one embodiment, as shown in FIG. 1A, stimulation source 12 includesan implantable pulse generator (IPG). An example IPG may be onemanufactured by Advanced Neuromodulation Systems, Inc., such as theGenesis® System, part numbers 3604, 3608, 3609, and 3644. In anotherembodiment, as shown in FIG. 1B, stimulation source 12 includes animplantable wireless receiver. An example wireless receiver may be onemanufactured by Advanced Neuromodulation Systems, Inc., such as theRenew®. System, part numbers 3408 and 3416. The wireless receiver iscapable of receiving wireless signals from a wireless transmitter 22located external to the person's body. The wireless signals arerepresented in FIG. 1B by wireless link symbol 24. A doctor, thepatient, or another user of stimulation source 12 may use a controller26 located external to the person's body to provide control signals foroperation of stimulation source 12. Controller 26 provides the controlsignals to wireless transmitter 22, wireless transmitter 22 transmitsthe control signals and power to the wireless receiver of stimulationsource 12, and stimulation source 12 uses the control signals to varythe stimulation parameters of electrical stimulation pulses transmittedthrough electrical stimulation lead 14 to the stimulation site. Anexample wireless transmitter 122 may be one manufactured by AdvancedNeuromodulation Systems, Inc., such as the Renew® System, part numbers3508 and 3516.

FIGS. 2A-2I illustrate example electrical stimulation leads 14 that maybe used to provide electrical stimulation to a target brain tissue site.As described above, each of the one or more leads 14 incorporated instimulation system 10 includes one or more electrodes 18 adapted to bepositioned near the target tissue site and used to deliver electricalstimulation energy to the target tissue site in response to electricalsignals received from stimulation source 12. A percutaneous lead 14,such as example leads shown in FIGS. 4A-4D, includes one or morecircumferential electrodes 18 spaced apart from one another along thelength of lead 14. An example of an eight-electrode percutaneous lead isan OCTRODE® lead manufactured by Advanced Neuromodulation Systems, Inc.A stimulation system such as is described in U.S. Pat. No. 6,748,276 isalso contemplated. Circumferential electrodes 18 emit electricalstimulation energy generally radially in all directions.

A laminotomy, paddle, or surgical stimulation lead 14, such as examplestimulation leads 14 described in FIGS. 2E-I, includes one or moredirectional stimulation electrodes 18 spaced apart from one anotheralong one surface of stimulation lead 14. An example of aneight-electrode, two column laminotomy lead is a LAMITRODE® and C-seriesLAMITRODE® 44 leads manufactured by Advanced Neuromodulation Systems,Inc. Directional stimulation electrodes 18 emit electrical stimulationenergy in a direction generally perpendicular to the surface ofstimulation lead 14 on which they are located.

Although various types of stimulation leads 14 are shown as examples,the present invention contemplates stimulation system 10 including anysuitable type of stimulation lead 14 in any suitable number. Inaddition, stimulation leads 14 may be used alone or in combination. Inaddition, the leads may be used alone or in combination. For example,unilateral stimulation of nerve tissue in the brain is typicallyaccomplished using a single lead 14 implanted in one side of the brain,while bilateral stimulation of the brain is typically accomplished usingtwo leads 14 implanted in opposite sides of the brain.

Whether using percutaneous leads, laminotomy leads, or some combinationof both, the leads are coupled to one or more conventionalneurostimulation devices, or signal generators. The devices can betotally implanted systems and/or radio frequency (RF) systems. Anexample of an RF system is a MNT/MNR-916CC system manufactured byAdvanced Neuromodulation Systems, Inc.

The preferred neurostimulation systems should allow each electrode ofeach lead to be defined as a positive, a negative, or a neutralpolarity. For each electrode combination (i.e., the defined polarity ofat least two electrodes having at least one cathode and at least oneanode), an electrical signal can have at least a definable amplitude(i.e., voltage), pulse width, and frequency, where these variables maybe independently adjusted to finely select the sensory transmittingnerve tissue required to inhibit transmission of neuronal signals.Generally, amplitudes, pulse widths, and frequencies are determinable bythe capabilities of the neurostimulation systems.

Voltage or intensity that can be used may include a range from about 1millivolt to about 1 volt or more, e.g., 0.1 volt to about 50 volts,e.g., from about 0.2 volt to about 20 volts and the frequency may rangefrom about 1 Hz to about 2500 Hz, e.g., about 1 Hz to about 1000 Hz,e.g., from about 2 Hz to about 100 Hz in certain embodiments. The pulsewidth may range from about 1 microsecond to about 2000 microseconds ormore, e.g., from about 10 microseconds to about 2000 microseconds, e.g.,from about 15 microseconds to about 1000 microseconds, e.g., from about25 microseconds to about 1000 microseconds. The electrical output may beapplied for at least about 1 millisecond or more, e.g., about 1 second,e.g., about several seconds, where in certain embodiments thestimulation may be applied for as long as about 1 minute or more, e.g.,about several minutes or more, e.g., about 30 minutes or more may beused in certain embodiments.

It is envisaged that the patient will require intermittent assessmentwith regard to patterns of stimulation. Different electrodes on the leadcan be selected by suitable computer programming, such as that describedin U.S. Pat. No. 5,938,690, which is incorporated by reference here infull. Utilizing such a program allows an optimal stimulation pattern tobe obtained at minimal voltages. This ensures a longer battery life forthe implanted systems.

In certain embodiments, the electrical stimulation system of the presentinvention includes a system that is capable of being programmed withthree or more stimulation settings to generate a corresponding number ofelectrical stimulation pulses. These and other objects of the system areobtained by providing a microcomputer controlled system. To control thestimulation setting and associated amplitude broadcast to the receiver,the transmitter includes a programmable setting time generator which iscontrolled by the microcomputer. The setting time generator generates atreatment interval which is sent to a programmable setting counter. Thetreatment interval is the interval that a particular stimulation settingis broadcast before the transmitter switches to the next stimulationsetting. In the “simultaneous” operations mode, the treatment modalityis set such that the patient cannot discern the switching betweenstimulation setting intervals, or pulses, and feels only the cumulativeeffect of all settings. The setting counter uses the treatment intervalto control the select lines of the setting and amplitude multiplexers.The counter allows the setting counter to cycle through the desiredstimulation settings substantially sequentially and ensures that allelected settings are broadcast. The system further includes a clock toprovide a signal at a continuous frequency. Similar systems are furtherdescribed in U.S. Pat. No. 6,609,031, U.S. Provisional Application No.60/561,437, entitled “Pulse Generator Circuit Universal Custom OutputDriver” filed Apr. 12, 2004, U.S. Provisional Application No.60/648,556, entitled “Efficient Fractional Voltage Converter” filed Jan.31, 2005, and U.S. Provisional Application No. 60/568,384, entitled“Multi-Programmable Trial Stimulator” filed May 5, 5, 2004, each ofwhich is incorporated herein by reference in its entirety.

III. Implantation of System

One technique that offers the ability to affect neuronal function is thedelivery of electrical stimulation for neuromodulation directly totarget tissues via an implanted system having an electrode. Theelectrode can also be comprised within a stimulation lead. The electrodeis coupled to system to stimulate the target site.

Techniques for implanting electrodes or stimulation leads such asstimulation lead 14 are known to those skilled in the art. In certainembodiments, for example, patients who are to have an electricalstimulation lead or electrode implanted into the brain, generally, firsthave a stereotactic head frame, such as the Leksell, CRW, or Compass,mounted to the patient's skull by fixed screws. However, framelesstechniques may also be used. Subsequent to the mounting of the frame,the patient typically undergoes a series of magnetic resonance imagingsessions, during which a series of two dimensional slice images of thepatient's brain are built up into a quasi-three dimensional map invirtual space. This map is then correlated to the three dimensionalstereotactic frame of reference in the real surgical field. In order toalign these two coordinate frames, both the instruments and the patientmust be situated in correspondence to the virtual map. The current wayto do this is to rigidly mount the head frame to the surgical table.Subsequently, a series of reference points are established to relativeaspects of the frame and patient's skull, so that either a person or acomputer software system can adjust and calculate the correlationbetween the real world of the patient's head and the virtual space modelof the patient MRI scans. The surgeon is able to target any regionwithin the stereotactic space of the brain with precision (e.g., within1 mm). Initial anatomical target localization is achieved eitherdirectly using the MRI images or functional imaging (PET or SPECTscan,fMRI, MSI), or indirectly using interactive anatomical atlas programsthat map the atlas image onto the stereotactic image of the brain. As isdescribed in greater detail elsewhere in this application, theanatomical targets or predetermined site or target site may bestimulated directly or affected through stimulation in another region ofthe brain.

FIG. 3 illustrates example placement of the electrical stimulationsystem 10 shown in FIGS. 1A-1B within a person's body 30. Electricalstimulation lead 14 is implanted under the person's skull 32 proximateor in communicate with a particular region of the person's brain. Incertain embodiments, electrical stimulation lead 14 is positioned withinthe extradural region adjacent the brain such that one or moreelectrodes 18 are located proximate target nerve tissue 34 within one ormore regions 38 of the brain, for example, the frontal lobe, theoccipital lobe, the parietal lobe, the temporal lobe, the cerebellum, orthe brain stem. More particularly, the target tissue 34 in the brain maybe located in one or more of the somatosensory cortex, moreparticularly, the primary somatosensory cortex or the secondarysomatosensory cortex or the somatosensory association complex, orassociated with the somatosensory cortex.

Additional target sites also include, but are not limited to thecerebellum, which can also be activated in sensory stimulation. Thus,other targets can also include any cortical region of the brainassociated or in communication with the sensory cortex, as well as anysubcortical region of the brain in association or communication with thesensory cortex. Regions of the brain that are in association with thesensory cortex includes the functional areas of the sensory cortex forexample, but not limited to the primary somatosensory cortex, thesecondary somatosensory cortex, the somatosensory association complex,primary visual cortex, secondary and tertiary visual cortices, visualassociation cortex, primary auditory cortex, auditory associationcortex, gustatory cortex, and vestibular cortex, other brain regionsthat receive somatic inputs, for example, the posterior parietal lobe,as well as any brain region that is stimulated by sensory stimulation,such as the cerebellum. Thus, stimulation of the sensory cortex includesthe somatosensory processing cortical regions of the brain andsub-cortical regions or structures, as well as the any brain region inwhich there are projection connections for example, the basal ganglia,the striatum, the motor cortex, the posterior parietal cortex, thethalamus (e.g., the ventral posterior nucleus of the thalamus),brainstem, dorsal column nuclei, and the spinal cord (e.g., dorsal hornof the spinal cord).

In certain embodiments, the target sites may include brain areas thatare known to be involved in pain perception for example the lateralthalamus, primary and second somatosensory regions, the insular cortex,the posterior parietal cortex, the prefrontal cortex, periaqueductalgrey, basal ganglia, supplementary motor cortex or area, and cerebellum.More particularly, the target sites may include the areas or regionsimplicated in pain inhibition, for example, but not limited toperiaqueductal grey, basal ganglia, supplementary motor cortex or area,and cerebellum.

Still further other target sites include, but are not limited to theputamen, the thalamus, the insula, the anterior cingulate cortex, thesupplementary motor area, the frontal operculum, the auditory cortex,such as the primary auditory cortex, AI, also known as the transversetemporal gyri of Heschl (Brodmann's areas 41 and 42), the secondaryauditory cortex, All (Brodmann's areas 22 and 52), the remote projectionregion, the ventral medial geniculate, which projects almost entirely toAI, the surrounding auditory areas, which receive projections from therest of the geniculate body, and the medial geniculate body, which isthe major auditory nucleus of the thalamus. Other target areas caninclude those identified by the methodology discussed below.

In certain embodiments, electrical stimulation lead 14 is located atleast partially within or below the dura mater proximate target tissue34. For example, electrical stimulation lead 14 may be inserted into thecortex or deeper layers of the brain.

Stimulation source 12 is implanted within a subcutaneous pocket withinthe person's torso 40 (such as in or near the chest area or buttocks),and connecting portion 16 is tunneled, at least in part, subcutaneouslyunderneath the person's skin to connect stimulation source 12 with theelectrical stimulation lead 14. However, stimulation source 12 may belocated at any suitable location within the person's body 30 accordingto particular needs.

FIG. 4 is a cross-section of a portion of the person' head shown in FIG.3, illustrating an example location of electrical stimulation lead 14.In certain embodiments, as discussed above, electrical stimulation lead14 is located in the extradural region 42 outside the dura mater 44 andproximate target nerve tissue 34 within one or more regions 38 of thebrain. In other embodiments, the electrical stimulation lead 14 islocated in an intradural region inside the dura mater and proximatetarget tissue within one or more regions of the brain.

In certain embodiments of the present invention, the target site orbrain region to be stimulated is determined using techniques thatmeasure altered neuronal activity in the brain. For example, the brainof an afflicted person is imaged or mapped using standard techniques todetermine altered neuronal activity includes overactive or underactiveactivity. The brain imaging information indicates whether the identifiedtarget tissue site or brain region is overactive or underactive and thedegree or intensity of such overactivity or underactivity. Techniquesused may include, for example, positron emission tomography (PET),magnetic resonance imaging (MRI), functional MRI (fMRI),electroencephalography (EEG), magnetoencephalography (MEG), x-raycomputed tomography (CT), single photon emission computed tomography(SPECT), brain electrical activity mapping (BEAM), transcranial magneticstimulation (TMS), electrical impedance tomography (EIT), near-infraredspectroscopy (NIRS), and optical imaging.

FIG. 5 illustrates an example method for determining an optimal locationand implanting or placing a stimulation system described above into aperson in order to electrically stimulate a target site.

In certain embodiments, the target brain tissue to be stimulated isidentified using standard brain mapping techniques, such as imagingtechniques, as well as other neurophysiological techniques such as EEG,MEG, nerve condition studies. Techniques used to map the brain mayinclude, for example, positron emission tomography (PET), magneticresonance imaging (MRI), functional MRI (fMRI), electroencephalography(EEG), magnetoencephalography (MEG), x-ray computed tomography (CT),single photon emission computed tomography (SPECT), brain electricalactivity mapping (BEAM), transcranial magnetic stimulation (TMS),electrical impedance tomography (EIT), near-infrared spectroscopy(NIRS), nerve condition studies, and optical imaging. For additionaldescription of identifying targets in a person's brain, see U.S.application Ser. No. 10/993,888, which is incorporated herein byreference in its entirety.

At step 100, at least a portion of the person's brain may be imagedand/or mapped to obtain neuronal information that identifies a targetsite in the brain having a notable level of activity, such asoveractivity or underactivity for example, which could be associatedwith a neurological condition. The utilization of techniques to map thebrain enables one of skill in the art to determine the area of the brainin which there is an altered neuronal activity. Such altered neuronalactivity can be associated with reorganization of neuronal cells, suchas cortical reorganization. The information obtained from these mapsprovide one of skill in the art with the knowledge of determining thebrain region that has an altered activity that is associated with aneurological condition or can be correlated with the neurologicalcondition. In certain embodiments, it is necessary to perform thesemapping studies to identify the target site so that the appropriatebrain region is stimulated to result in treatment of the neurologicalcondition without such mapping it may be difficult to determine thebrain region to stimulate to achieve the optimum benefit from theelectrical stimulation.

Those in the art will understand that this technique may be used asconfirmation or investigation of the notable level of activity of thetarget tissue. Additionally, those in the art will understand that thelocation of the target tissue in the person's brain may be determinedusing information from brain imaging studies performed on otherpatients, and thus the imaging of the person's brain at step 100 may notbe performed. Such brain imaging studies may include imaging informationobtained using one or more of the imaging techniques listed above toimage the brains of patients suffering from various types ofneurological conditions. The location of tissue in the brain correlatingto various conditions may be identified using statistical analysis ofsuch mapping information (imaging and/or neurophysiological studies).Thus, at step 100, target tissue in the person's brain correlated to theneurological condition may be identified according to the results ofsuch brain imaging studies.

At step 102, the brain imaging information obtained at step 100 (whetherfrom imaging the person's brain or from imaging studies of otherpatients suffering from the same or similar condition as the person) isdownloaded into a neuronavigation system.

At step 104, TMS of the an area of the person's brain, such as an areaproximate the target brain tissue identified at step 100 for example,may be performed to determine whether the person is a candidate forreceiving an implanted electrical stimulation system 10. The TMSprocess, which is a non-invasive technique of activating or deactivatingfocal areas of the brain, may be guided by the navigation system thatincludes the brain imaging information obtained at step 100. If the TMSprocess is successful in treating the condition in the person's body,the person may be considered for receiving an implanted electricalstimulation system 10. Those of skill in the art realize that step 104is not essential. In fact, in certain embodiments of the presentinvention, the method skips step 104. Thus, the sequence is step 102directly to step 106.

Electrical stimulation system 10 is implanted or placed inside theperson at steps 106 through 118. At step 106, the skull 32 is firstprepared by exposing the skull 32 and creating a burr hole in the skull32. A burr hole cover may be seated within the burr hole and fixed tothe scalp or skull 32. Stereotactic equipment suitable to aid inplacement of an electrical stimulation lead 14 in the brain may bepositioned around the head. An insertion cannula for electricalstimulation lead 14 may be inserted through the burr hole into the brainat step 108, but a cannula is not typically used where lead 14 is alaminotomy or paddle lead 14. A cannula and electrical stimulation lead14 may be inserted together or lead 14 may be inserted through thecannula after the cannula has been inserted. Guided by the navigationsystem that includes the brain imaging information obtained at step 100,electrical stimulation lead 14 is precisely positioned proximate thebrain at step 110 such that one or more electrodes 18 are locatedproximate the target nerve tissue in the brain identified at step 100.In certain embodiments, electrical stimulation lead 14 is positionedextradurally, such as shown in FIG. 4.

At step 112, stimulation source 12 is activated, which generates andsends electrical stimulation pulses via electrical stimulation lead 14to the target nerve tissue proximate one or more electrodes 18 onstimulation lead 14. The electrical stimulation pulses delivered to thetissue by electrodes 18 may adjust the activity of the target tissue inan appropriate manner to treat the neurological condition. For example,if the brain imaging information obtained at step 100 indicates that theidentified target tissue is overactive, stimulation source 12 maygenerate, and the one or more electrodes 18 may deliver, appropriateelectrical stimulation pulses to decrease the activity of the targettissue proximate the one or more electrodes 18 to treat the neurologicalcondition. Similarly, if the brain imaging information obtained at step100 indicates that the identified target nerve tissue is underactive,stimulation source 12 may generate, and the one or more electrodes 18may deliver, appropriate electrical stimulation pulses to increase theactivity of the target nerve tissue proximate the one or more electrodes18 to treat the neurological condition.

At step 114, the person indicates whether the condition in the person'sbody is adequately alleviated by electrical stimulation system 10. Ifthe condition is not adequately alleviated, electrical stimulation lead14 may be moved incrementally at step 116 until the person indicatesthat the condition is adequately alleviated. Once electrical stimulationlead 14 has been positioned in the brain, lead 14 is uncoupled from anystereotactic equipment if present, and the cannula and stereotacticequipment if used are removed. Where stereotactic equipment is used, thecannula may be removed before, during, or after removal of thestereotactic equipment. Connecting portion 16 of electrical stimulationlead 14 is laid substantially flat along the skull. Where appropriate,any burr hole cover seated in the burr hole may be used to secureelectrical stimulation lead 14 in position and possibly to help preventleakage from the burr hole and entry of contaminants into the burr hole.Example burr hole covers that may be appropriate in certain embodimentsare illustrated and described in co-pending U.S. Application Nos.60/528,604 and 60/528,689, both filed Dec. 11, 2003 and entitled“Electrical Stimulation System and Associated Apparatus for Securing anElectrical Stimulation Lead in Position in a Person's Brain”, both ofwhich are incorporated herein in their entirety.

Once electrical stimulation lead 14 has been inserted and secured,stimulation source 12 is implanted at step 120. The implant site istypically a subcutaneous pocket formed to receive and house stimulationsource 12. The implant site is usually positioned a distance away fromthe insertion site, such as near the chest area or buttocks or anotherplace in the torso 40. Connecting portion 16 of lead 14 extends from thelead insertion site to the implant site at which stimulation source 12is implanted. A doctor, the patient, or another user of stimulationsource 12 may directly or indirectly input stimulation parameters forcontrolling the nature of the electrical stimulation provided. Stillfurther, the stimulation parameters can be adjusted accordingly tomaintain or achieve the optimum benefit. Such adjustments may requireproviding neuroplasticity signals or altered signals, increase thesignals or enhance the signals, etc. See the below discussion ofneuroplasticity, which is incorporated herein. Still further,adjustments can be made by increasing the amount of signals, forexample, stimulating more than one location in the brain as described inU.S. Provisional Application No. 60/645,405 entitled “ElectricalStimulation System and Method for Stimulating Multiple Locations ofTarget Nerve Tissue in the Brain to Treat Multiple Conditions in theBody” filed Jan. 19, 2005, and U.S. Pat. No. 6,609,031 each of which isincorporated herein by reference in its entirety.

Although example steps are illustrated and described, the presentinvention contemplates two or more steps taking place substantiallysimultaneously or in a different order. In addition, the presentinvention contemplates using methods with additional steps, fewer steps,or different steps, so long as the steps remain appropriate for imagingthe brain of a person suffering from a condition—or using brain imagingstudies regarding patients suffering from the same or similar conditionas the person—to identify target nerve tissue having a notable level ofactivity and implanting an example stimulation system 10 into a personfor electrical stimulation of the person's brain to adjust the level ofactivity in identified target tissue in the person's brain to treat theperson's condition.

IV. Methods to Treat Neurological Disorders

The present invention utilizes a stimulation system to alter neuronalactivity in the brain. More particularly, the stimulation system can beused to stimulate the brain and cause/allow the brain to act in the bestinterest of the host through use of the brain's natural mechanisms.

The present disclosure describes apparatuses and systems for applyingelectrical stimulation to cortical and other sites on a patient.Stimulation systems and methods described herein may be used to treat avariety of neurological conditions. Depending on the nature of aparticular condition, neural stimulation applied or delivered inaccordance with various embodiments of such systems and/or methods mayfacilitate or effectuate reorganization of interconnections or synapsesbetween neurons to (a) provide at least some degree of recovery of alost function; and/or (b) develop one or more compensatory mechanisms toat least partially overcome a functional deficit. Such reorganization ofneural interconnections may be achieved, at least in part, by a changein the strength of synaptic connections through a process thatcorresponds to a mechanism commonly known as Long-Term Potentiation(LTP). Electrical stimulation applied to one or more target neuralpopulations either alone or in conjunction with behavioral activitiesand/or adjunctive or synergistic therapies may facilitate or effectuateneural plasticity and the reorganization of synaptic interconnectionsbetween neurons.

Accordingly, the present invention relates to modulation of neuronalactivity to affect neurological, neuropsychological or neuropsychiatricactivity. The present invention finds particular application in themodulation of neuronal function or processing to affect a functionaloutcome. The modulation of neuronal function is particularly useful withregard to the prevention, treatment, or amelioration of neurological,psychiatric, psychological, conscious state, behavioral, mood, andthought activity (unless otherwise indicated these will be collectivelyreferred to herein as “neurological activity” which includes“psychological activity” or “psychiatric activity”). When referring to apathological or undesirable condition associated with the activity,reference may be made to a neurological disorder which includes“psychiatric disorder” or “psychological disorder” instead ofneurological activity or psychiatric or psychological activity. Althoughthe activity to be modulated usually manifests itself in the form of adisorder such as a attention or cognitive disorders (e.g., AutisticSpectrum Disorders); mood disorder (e.g., major depressive disorder,bipolar disorder, and dysthymic disorder) or an anxiety disorder (e.g.,panic disorder, posttraumatic stress disorder, obsessive-compulsivedisorder and phobic disorder); neurodegenerative diseases (e.g.,multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis(ALS), Parkinson's disease, Huntington's Disease, Guillain-Barresyndrome, myasthenia gravis, and chronic idiopathic demyelinatingdisease (CID)), movement disorders (e.g., dyskinesia, tremor, dystonia,chorea and ballism, tic syndromes, Tourette's Syndrome, myoclonus,drug-induced movement disorders, Wilson's Disease, ParoxysmalDyskinesias, Stiff Man Syndrome and Akinetic-Ridgid Syndromes andParkinsonism), epilepsy, tinnitus, pain, phantom pain, diabetesneuropathy, one skilled in the art appreciates that the invention mayalso find application in conjunction with enhancing or diminishing anyneurological or psychiatric function, not just an abnormality ordisorder. Neurological activity that may be modulated can include, butnot be limited to, normal functions such as alertness, conscious state,drive, fear, anger, anxiety, repetitive behavior, impulses, urges,obsessions, euphoria, sadness, and the fight or flight response, as wellas instability, vertigo, dizziness, fatigue, fotofobia, fonofobia,concentration dysfunction, memory disorders, symptoms of traumatic braininjury (whether physical, emotional, social or chemical), autonomicfunctions, which includes sympathetic and/or parasympathetic functions(e.g., control of heart rate), somatic functions, and/or entericfunctions.

In certain embodiments, neurological disorders or conditions that can betreated using the present invention include, for example, but are notlimited to cardiovascular diseases, e.g., atherosclerosis, coronaryartery disease, hypertension, hyperlipidemia, cardiomyopathy, volumeretention; neuroinflammatory diseases, e.g., viral meningitis, viralencephalitis, fungal meningitis, fungal encephalitis, multiplesclerosis, charcot joint; myasthenia gravis; orthopedic diseases, e.g.,osteoarthritis, inflammatory arthritis, reflex sympathetic dystrophy,Paget's disease, osteoporosis; lymphoproliferative diseases, e.g.,lymphoma, lymphoproliferative disease, Hodgkin's disease; autoimmunediseases, e.g., Graves disease, hashimoto's, takayasu's disease,kawasaki's diseases, arthritis, scleroderma, CREST syndrome, allergies,dermatitis, Henoch-schlonlein purpura, goodpasture syndrome, autoimmunethyroiditis, myasthenia gravis, Reiter's disease, lupus, rheumatoidarthritis; inflammatory and infectious diseases, e.g., sepsis, viral andfungal infections, wound healing, tuberculosis, infection, humanimmunodeficiency virus; pulmonary diseases, e.g., tachypnea, fibroticdiseases such as cystic fibrosis, interstitial lung disease,desquamative interstitial pneumonitis, non-specific interstitialpneumonitis, lymphocytic interstitial pneumonitis, usual interstitialpneumonitis, idiopathic pulmonary fibrosis; transplant related sideeffects such as rejection, transplant-related tachycardia, renalfailure, typhlitis; transplant related bowel dysmotility,transplant-related hyperreninemia; sleep disorders, e.g., insomnia,obstructive sleep apnea, central sleep apnea; gastrointestinaldisorders, e.g., hepatitis, xerostomia, bowel dysmotility, peptic ulcerdisease, constipation, post-operative bowel dysmotility; inflammatorybowel disease; endocrine disorders, e.g., hypothyroidism, hyperglycemia,diabetes, obesity, syndrome X; cardiac rhythm disorders, e.g., sicksinus syndrome, bradycardia, tachycardia, QT interval prolongationarrhythmias, atrial arrhythmias, ventricular arrhythmias; genitourinarydisorders, e.g., bladder dysfunction, renal failure, hyperreninemia,hepatorenal syndrome, renal tubular acidosis, erectile dysfunction;cancer; fibrosis; skin disorders, e.g., wrinkles, cutaneous vasculitis,psoriasis; aging associated diseases and conditions, e.g., shy dragers,multi-system atrophy, osteoporosis, age related inflammation conditions,degenerative disorders; autonomic dysregulation diseases; e.g.,headaches, concussions, post-concussive syndrome, coronary syndromes,coronary vasospasm; neurocardiogenic syncope; neurologic diseases suchas epilepsy, seizures, stress, bipolar disorder, migraines and chronicheadaches; conditions related to pregnancy such as amniotic fluidembolism, pregnancy-related arrhythmias, fetal stress, fetal hypoxia,eclampsia, preeclampsia; conditions that cause hypoxia, hypercarbia,hypercapnia, acidosis, acidemia, such as chronic obstructive lungdisease, emphysema, cardiogenic pulmonary edema, non-cardiogenicpulmonary edema, neurogenic edema, pleural effusion, adult respiratorydistress syndrome, pulmonary-renal syndromes, interstitial lungdiseases, pulmonary fibrosis, and any other chronic lung disease; suddendeath syndromes, e.g., sudden infant death syndrome, sudden adult deathsyndrome; vascular disorders, e.g., acute pulmonary embolism, chronicpulmonary embolism, deep venous thrombosis, venous thrombosis, arterialthrombosis, coagulopathy, aortic dissection, aortic aneurysm, arterialaneurysm, myocardial infarction, coronary vasospasm, cerebral vasospasm,mesenteric ischemia, arterial vasospasm, malignant hypertension; primaryand secondary pulmonary hypertension, reperfusion syndrome, ischemia,cerebral vascular accident, cerebral vascular accident and transientischemic attacks; pediatric diseases such as respiratory distresssyndrome; bronchopulmonary dysplasia; Hirschprung disease; congenitalmegacolon, aganglionosis; ocular diseases such as glaucoma; and thelike.

The present invention finds particular utility in its application tohuman neurological disorders, for example psychological or psychiatricactivity/disorder and/or physiological disorders and/or otherneurological conditions. One skilled in the art appreciates that thepresent invention is applicable to other animals which exhibit behaviorthat is modulated by the neuronal tissue. This may include, for example,primates, canines, felines, horses, elephants, dolphins, etc. Utilizingthe various embodiments of the present invention, one skilled in the artmay be able to modulate neuronal functional outcome to achieve adesirable result.

One technique that offers the ability to affect neuronal function is thedelivery of electrical and/or ultrasonic and/or magnetic stimulation forneuromodulation directly to target tissues or predetermined tissue sitesvia an implanted device having a probe. The probe can be stimulationlead or electrode assembly. The electrode assembly may be one electrode,multiple electrodes, or an array of electrodes in or around the targetarea. The proximal end of the probe is coupled to a system to operatethe device to stimulate the target site. Thus, the probe is coupled toan electrical signal source, which, in turn, is operated to stimulatethe target tissue or predetermined site.

Treatment regimens may vary as well, and often depend on the health andage of the patient. Obviously, certain types of disease will requiremore aggressive treatment, while at the same time, certain patientscannot tolerate more taxing regimens. The clinician will be best suitedto make such decisions based on the known subject's history.

The therapeutic system or of the present invention is surgicallyimplanted in the subject's body as described herein. One of skill in theart is cognizant that a variety of electrodes or electrical stimulationleads may be utilized in the present invention. It is desirable to usean electrode or lead that contacts or conforms to the target site foroptimal delivery of electrical stimulation. One such example, is asingle multi contact electrode with eight contacts separated by 21/2 mmeach contract would have a span of approximately 2 mm. Another exampleis an electrode with two 1 cm contacts with a 2 mm intervening gap. Yetfurther, another example of an electrode that can be used in the presentinvention is a 2 or 3 branched electrode to cover the target site. Eachone of these three pronged electrodes have four contacts 1-2 mm contactswith a center to center separation of 2 of 2.5 mm and a span of 1.5 mm

According to one embodiment of the present invention, the target site isstimulated using stimulation parameters such as, pulse width of about 1to about 500 microseconds, more preferable, about 1 to about 90microseconds; frequency of about 1 to about 300 Hz, more preferably,about 100 to about 185 Hz; and voltage of about 0.1 to about 10 volts,more preferably about 1 to about 10 volts. It is known in the art thatthe range for the stimulation parameters may be greater or smallerdepending on the particular patient needs and can be determined by thephysician. Other parameters that can be considered may include the typeof stimulation for example, but not limited to acute stimulation,subacute stimulation, and/or chronic stimulation.

Using the stimulation system of the present invention, the predeterminedsite or target area is stimulated in an effective amount or effectivetreatment regimen to decrease, reduce, modulate or abrogate theneurological disorder. Thus, a subject is administered a therapeuticallyeffective stimulation so that the subject has an improvement in theparameters relating to the neurological disorder or condition includingsubjective measures such as, for example, neurological examinations andneuropsychological tests (e.g. Minn. Multiphasic Personality Inventory,Beck Depression Inventory, Mini-Mental Status Examination (MMSE),Hamilton Rating Scale for Depression, Wisconsin Card Sorting Test(WCST), Tower of London, Stroop task, MADRAS, CGI, N-BAC, or Yale-BrownObsessive Compulsive score (Y-BOCS)), motor examination, and cranialnerve examination, and objective measures including use of additionalpsychiatric medications, such as anti-depressants, or other alterationsin cerebral blood flow or metabolism and/or neurochemistry.

Patient outcomes may also be tested by health-related quality of life(HRQL) measures: Patient outcome measures that extend beyond traditionalmeasures of mortality and morbidity, to include such dimensions asphysiology, function, social activity, cognition, emotion, sleep andrest, energy and vitality, health perception, and general lifesatisfaction. (Some of these are also known as health status, functionalstatus, or quality of life measures.)

Functional imaging may also be used to measure the effectiveness of thetreatment. This includes electrical methods such aselectroencephalography (EEG), magnetoencephalography (MEG), singlephoton emission computed tomography (SPECT), as well as metabolic andblood flow studies such as functional magnetic resonance imaging (fMRI),and positron emission tomography (PET) which can be utilized to localizebrain function and dysfunction. Also, electrophysiological examinations,such as electromyography (EMG) and nerve conduction studies (NCS), canalso be utilized to assess the effectiveness of the treatment.

Clinical observations may indicate that the efficacy of treatment may becorrelated to the amplitude or intensity. For example, stimulation ofthe somatosensory cortex may include stimulation parameters that aresub-threshold. In the treatment of pain, the intensity or amplitude ofthe electrical stimulation of the somatosensory cortex is sub-thresholdas to be beneficial to alleviate pain and not exacerbate the paincondition.

In certain embodiments, it may be necessary to monitor the stimulationsignals or parameters in the instance that adjustments need to be madeto obtain the optimum benefit of the stimulation system. Such monitoringmay be performed by the subject or a clinician. Monitoring may includeobserving any changes in symptoms or any other clinical observations, aswell as performing neurophysiological studies, neurologicalexaminations, psychological examinations, functional imaging studies,etc. Based upon the information obtained from this type of monitoring,the stimulation parameters or signals may be adjusted if necessary.

Thus, stimulation signals or the series of electrical or magnetic pulsesused can affect neurons within a target neural population. Stimulationsignals may be defined or described in accordance with stimulationsignal parameters that include pulse amplitude, pulse frequency, dutycycle, stimulation signal duration, and/or other parameters. Electricalor magnetic stimulation signals applied to a population of neurons candepolarize neurons within the population toward their thresholdpotentials. Depending upon stimulation signal parameters, thisdepolarization can cause neurons to generate or fire action potentials.

Neural stimulation that elicits or induces action potentials in afunctionally significant proportion of the neural population to whichthe stimulation is applied is referred to as supra-thresholdstimulation; neural stimulation that fails to elicit action potentialsin a functionally significant proportion of the neural population isdefined as sub-threshold stimulation. In general, supra-thresholdstimulation of a neural population triggers or activates one or morefunctions associated with the neural population, but sub-thresholdstimulation by itself does not trigger or activate such functions.Supra-threshold neural stimulation can induce various types ofmeasurable or monitorable responses in a patient. For example,supra-threshold stimulation applied to a patient's motor cortex caninduce muscle fiber contractions in an associated part of the body toproduce an intended type of therapeutic, rehabilitative, or restorativeresult. Still further, sub-threshold stimulation applied to a patient'ssomatosensory cortex can alleviate pain without inducing paresthesia,which is a sensation of numbness or tingling.

For purposes of this invention, beneficial or desired clinical resultsinclude, but are not limited to, alleviation of symptoms, improvement ofsymptoms, diminishment of extent of disease, stabilized (i.e., notworsening) state of disease, delay or slowing of disease progression,amelioration or palliation of the disease state, and remission (whetherpartial or total), whether objective or subjective. The improvement isany observable or measurable improvement. Thus, one of skill in the artrealizes that a treatment may improve the patient condition, but may notbe a complete cure of the condition or disease.

In certain embodiments, in connection with improvement in one or more ofthe above or other neurological disorders, the electrical stimulationmay have a “brightening” effect on the person such that the person looksbetter, pain-free, feels better, moves better, thinks better, andotherwise experiences an overall improvement in quality of life.

The present invention relates to methods of affecting pain (e.g.,chronic pain) to regulate, prevent, treat, alleviate the symptoms ofand/or reduce the effects of pain. Although not wishing to be bound toany particular definition or characterization, chronic pain cangenerally be characterized as being nociceptive or non-nociceptive pain.Nociceptive pain, also referred to as somatic pain, involves directactivation of the nociceptors, such as mechanical, chemical, and thermalreceptors, found in various tissues, such as bone, muscle, vessels,viscera, and cutaneous and connective tissue. The afferent somatosensorypathways are thought to be intact in nociceptive pain and examples ofsuch pain include cancer pain from bone or tissue invasion, non-cancerpain secondary to degenerative bone and joint disease or osteoarthritis,and failed back surgery. The foregoing examples of nociceptive pain arein no way limiting and the methods of the present invention encompassmethods of affecting all types of nociceptive pain.

Non-nociceptive pain, also referred to as neuropathic pain, ordeafferentation pain, occurs in the absence of activation of peripheralnociceptors. Non-nociceptive pain often results from injury ordysfunction of the central or peripheral nervous system. Such damage mayoccur anywhere along the neuroaxis and includes thalamic injury orsyndromes (also referred to as central pain, supraspinal central pain,or post-stroke pain); stroke; traumatic or iatrogenic trigeminal(trigeminal neuropathic) brain or spinal cord injuries; phantom limb orstump pain; postherpetic neuralgia; anesthesia dolorosa; brachial plexusavulsion; complex regional pain syndrome I and II; postcordotomydysesthesia; and various peripheral neuropathies. The foregoing examplesof non-nociceptive pain are in no way limiting and the methods of thepresent invention encompass methods of affecting all types ofnon-nociceptive pain.

In certain embodiments, stimulation of the target brain tissue may beprovided to effectively treat pain, for example chronic pain, acutepain, or subacute pain, deafferentation pain, phantom pain, or any othertype of sensory input that is related to pain or any type of alteredsensory input or altered sensory perception.

Chronic pain is difficult to treat. After development of the adultsomatotopic representation, any alteration of the normal sensory input(either increase or decrease) leads to a reorganization of the entiresomatosensory tract. This occurs daily throughout life under influenceof environmental stimuli (Kandel, 1991; Yuste and Sur, 1999). Thus, anytype of event in the person's life can result in alterations in thisreorganization. For example, phantom pain and phantom sensations areassociated with somatosensory cortex reorganization (Flor, 2003; Flor etal., 1995; Peyron et al., 2000), such that the cortical area originallycorresponding to the amputated limb is taken over by sensory input fromadjacent areas on Penfield's somatosensory homunculus (Pons et al.,1991). Furthermore magnetoecephalographic studies have shown a clearcorrelation between the amount of phantom pain and the extend ofcortical reorganization (Flor et al., 1995).

In the somatosensory system, this reorganization seems to occur in twophases (Pons et al., 1991; Doetsch et al., 1996). Peripherally inducedand maintained reorganization is initiated immediately after injury ortraining (Doetsch et al., 1996; Wiech et al., 2000). This first phaseencompasses minutes to weeks and leads to axonal growth and synapticsprouting. If maintained by peripheral input in a second phase permanentcortical, thalamothalamic or corticothalamic connections occur (Pons etal., 1991, Wieh et al., 2000) leading to intractable phantom limb pain.Changes in peripheral input afterwards do not affect the changes of thesecond phase (Wiech et al., 2000). This explains why the phantom painbecomes very difficult to treat once it exists for more than 6 months(Ramachandran and Hirstein, 1998).

Thus, the stimulation system and method used in the present alters ormodulates this cortical reorganization to treat pain. The presentinvention utilizes techniques similar to the ones described in U.S.application Ser. No. 10/993,888, which is incorporated herein byreference in its entirety, as well as the techniques described in DeRidder et al., 2004. The technique involves mapping the brain mappingusing standard functional neuroimaging techniques such as PET scan, fMRIor MSI to determine a target area, for example, the area of the brainpossessing reorganization. Once target area or area of reorganization isdetermined, then an electrode, for example a cortex lead, can beimplanted extradurally in communication with the target area.

Still further, in certain embodiments, stimulation of a target braintissue site may be provided to effectively treat fibromyalgia or otherdiffuse pain in any one or more regions of the body.

In certain embodiments, stimulation of the target brain tissue site mayeffectively treat one or more neurological disorder associated withtraumatic brain injury (TBI). Physiological conditions associated withTBI that may be treated effectively through stimulation of a braintissue site include, for example, intractable localized, diffuse, orother pain in the head, neck, shoulders, upper extremities, or low back,fibromyalgia or other diffuse pain in one or more regions of the body,or other pain symptoms. Instead or in addition to such physiologicalconditions, psychological and other conditions associated with TBI thatmay be treated effectively through stimulation of the target braintissue include, for example, intractable nausea (e.g., fromgastroparesis), sleep disorders, chronic fatigue, behavioralmodifications (e.g., lassitude, reduced motivation, depression,emotional distress, irritability, aggression, anxiety, erratic moodswings, personality changes, and loss of enjoyment), sexual dysfunction,and other conditions. Instead or in addition to physiological,psychological, and other conditions such as those described above,conditions associated with TBI that may be treated effectively throughstimulation of the target brain tissue include decreased cognitivefunctioning in the form of, for example, impaired memory (e.g.,short-term memory, visual memory, and auditory memory), reducedattention and concentration, and reduced information processing capacity(e.g., learning capacity, ability to process complex information,ability to operate simultaneously on different information, ability torapidly shift attention, ability to plan and sequence, visuomotorcapability, auditory language comprehension, and verbal fluency).

V. Programming of the Stimulation System

During the operation of stimulation system 10 according to a particularset of stimulation parameters, the efficacy of the stimulationassociated with the particular set of stimulation parameters maydecrease over time due to neuroplasticity of the brain. Neuroplasticityrefers to the ability of the brain to dynamically reorganize itself inresponse to certain stimuli to form new neural connections. This allowsthe neurons in the brain to compensate for injury or disease and adjusttheir activity in response to new situations or changes in theirenvironment. With respect to electrical stimulation, the reduction inefficacy due to neuroplasticity can occur after just a few weeks oftreatment. In order to regain the same efficacy, a new set ofefficacious electrical stimulation parameters must be determined, thenew set of parameters must be entered into the system, and the system isagain used to electrically stimulate the brain according to the new setof parameters to continue to treat the condition. This may result in theadditional time and expense associated with a return visit to thetreating physician for determining and entering the new set ofparameters. Especially where treatment is to continue over a relativelylong period of time, such as months or years, this additional time andexpense poses a significant drawback.

Thus, in certain embodiments, in addition to providing therapeuticelectrical stimulation to the brain for treating the condition in theperson's body, stimulation system 10 may be capable of applyingadditional electrical stimulation to the brain to reduce neuroplasticityeffects associated with the therapeutic electrical stimulation asdescribed in U.S. application Ser. No. 10,994,008 entitled “ElectricalStimulation System, lead and Method Providing Reduced NeuroplasticityEffects,” which is incorporated herein by reference in its entirety.

In one embodiment, the nature of the neuroplasticity reducing electricalstimulation may be varied more or less continually, in a predeterminedor randomized manner, to prevent, delay, or otherwise reduce the abilityof the brain to adapt to the neuroplasticity reducing electricalstimulation and dynamically reorganize itself accordingly. In a moreparticular embodiment, the neuroplasticity reducing electricalstimulation may be randomized or otherwise varied about the therapeuticelectrical stimulation to achieve this result. In essence, therandomized or otherwise varied neuroplasticity reducing electricalstimulation makes it more difficult for the brain to dynamicallyreorganize itself to overcome the effects of the therapeutic electricalstimulation.

In certain other embodiments, stimulation system 10 may similarly becapable of applying additional electrical stimulation to the brain toenhance, rather than reduce, neuroplasticity effects associated with thetherapeutic electrical stimulation. In one embodiment, the nature of theneuroplasticity enhancing electrical stimulation may controlled in apredetermined non-randomized manner to promote, accelerate, or otherwiseenhance the ability of the brain to adapt to the neuroplasticityenhancing electrical stimulation and dynamically reorganize itselfaccordingly. In essence, the predetermined non-randomizedneuroplasticity enhancing electrical stimulation facilitates the braindynamically reorganizing itself in response to the therapeuticelectrical stimulation. It should be understood that techniquesanalogous to some or all of those discussed below for reducingneuroplasticity effects may be employed for enhancing neuroplasticityeffects.

FIG. 6 illustrates an example stimulation set 150. One or morestimulation sets 150 may be provided, each stimulation set 150specifying a number of stimulation parameters for the stimulation set150. For example, as described more fully below with reference to FIGS.7-8, multiple stimulation sets 150 may be executed in an appropriatesequence according to a pre-programmed or randomized stimulationprogram. Stimulation parameters for a stimulation set 150 may include anamplitude or intensity, a frequency, phase information, and a pulsewidth for each of a series of stimulation pulses that electrodes 18 areto deliver to the target nerve tissue during a time interval duringwhich stimulation set 150 is executed, along with a polarity 152 foreach electrode 18 within each stimulation pulse. In general, electricfields are generated between adjacent electrodes 18 having differentpolarities 152 to deliver electrical stimulation pulses to nerve tissue.Stimulation parameters may also include a pulse shape, for example,biphasic cathode first, biphasic anode first, or any other suitablepulse shape.

For reducing neuroplasticity effects associated with therapeuticelectrical stimulation, one or more stimulation parameters for astimulation set 150 may be randomized or otherwise varied in anysuitable manner within the time interval in which stimulation set 150 isexecuted, spanning one or more stimulation pulses within eachstimulation pulse. For example, instead of or in addition to randomizingor otherwise varying polarities 152 for electrodes 18 as describedbelow, the amplitude or intensity, frequency, phase information, andpulse width may be randomized or otherwise varied within predeterminedranges, singly or in any suitable combination, within each stimulationpulse. As another example, instead of or in addition to randomizing orotherwise varying polarities 152 for electrodes 18 over multiplestimulation pulses as described more fully below, the amplitude orintensity, frequency, phase information, and pulse width may berandomized or otherwise varied within predetermined ranges, singly or inany suitable combination, over multiple stimulation pulses, where thecombination of stimulation parameters is substantially constant withineach stimulation pulse but different for successive stimulation pulses.Such randomization or other variation of stimulation parameters for astimulation set 150 reduces the ability of the brain to adapt to theneuroplasticity reducing electrical stimulation and dynamicallyreorganize itself to overcome the effects of the neuroplasticityreducing stimulation.

The polarity for an electrode 18 at a time 154 beginning a correspondingstimulation pulse or sub-interval within a stimulation pulse may be arelatively positive polarity 152, a relatively negative polarity 152, oran intermediate polarity 152 between the relatively positive polarity152 and relatively negative polarity 152. For example, the relativelypositive polarity 152 may involve a positive voltage, the relativelynegative polarity 152 may involve a negative voltage, and the relativelyintermediate polarity 152 may involve a zero voltage (i.e. “highimpedance”). As another example, the relatively positive polarity 152may involve a first negative voltage, the relatively negative polarity152 may involve a second negative voltage more negative than the firstnegative voltage, and the relatively intermediate polarity 152 mayinvolve a negative voltage between the first and second negativevoltages. The availability of three distinct polarities 152 for anelectrode 18 may be referred to as “tri-state” electrode operation. Thepolarity 152 for each electrode 18 may change for each of the sequenceof times 154 corresponding to stimulation pulses or to sub-intervalswithin a stimulation pulse according to the stimulation parametersspecified for the stimulation set 150. For example, as is illustrated inFIG. 6 for an example stimulation set 150 for a lead 14 with sixteenelectrodes 18, the polarities 152 of the sixteen electrodes 18 maychange for each of the sequence of times 154. In the example of FIG. 6,a relatively positive polarity 152 is represented using a “1,” arelatively intermediate polarity 152 is represented using a “0,” and arelatively negative polarity 152 is represented using a “−1,” althoughany suitable values or other representations may be used.

Where appropriate, the polarity 152 for each electrode 18 may change ina predetermined or randomized manner, randomized changes possibly beingmore effective with respect to any neuroplasticity reducing stimulationfor reasons described above.

Where stimulation system 10 provides, in addition to therapeuticelectrical stimulation, electrical stimulation to reduce neuroplasticityeffects associated with the therapeutic electrical stimulation, eachstimulation pulse or sub-interval within a stimulation pulse may beparticular to the stimulation being provided; that is, either totherapeutic electrical stimulation or to neuroplasticity reducingelectrical stimulation. For example, one or more stimulation pulses orsub-intervals may be designed to provide therapeutic electricalstimulation and one or more other stimulation pulses or sub-intervalsmay be designed to reduce neuroplasticity effects. In this case, thetherapeutic stimulation pulses or sub-intervals and neuroplasticityreducing stimulation pulses or sub-intervals may be arranged temporallyin any suitable manner. A therapeutic stimulation pulse or sub-intervalmay be separated from a successive therapeutic stimulation pulse orsub-interval by any number of neuroplasticity reducing stimulationpulses or sub-intervals and this number may be the same between eachpair of therapeutic stimulation pulses or sub-intervals or may varybetween each pair of therapeutic stimulation pulses or sub-intervals ina predetermined or randomized manner. As another example, one or morestimulation pulses or sub-intervals may be designed to concurrentlyprovide both-therapeutic and neuroplasticity reducing electricalstimulation.

Similarly, where stimulation system 10 provides, in addition totherapeutic electrical stimulation, electrical stimulation to reduceneuroplasticity effects associated with the therapeutic electricalstimulation, each stimulation set 150 may be particular to either thetherapeutic electrical stimulation or the neuroplasticity reducingelectrical stimulation. For example, one or more stimulation sets 150may be designed to provide therapeutic electrical stimulation and one ormore other stimulation sets 150 may be designed to reduceneuroplasticity effects. In this case, the therapeutic stimulation sets150 and neuroplasticity reducing stimulation sets 150 may be arrangedtemporally in any suitable manner. A therapeutic stimulation set 150 maybe separated from a successive therapeutic stimulation set 150 by anynumber of neuroplasticity reducing stimulation sets 150 and this numbermay be the same between each pair of therapeutic stimulation sets 150 ormay vary between each pair of therapeutic stimulation sets 150 in apredetermined or randomized manner. As another example, one or morestimulation sets 150 may be designed to concurrently provide boththerapeutic and neuroplasticity reducing electrical stimulation.

In addition, the amplitude or intensity, frequency, phase information,or pulse width for a stimulation set 150 may be particular to thestimulation being provided. For example, therapeutic electricalstimulation may be provided using higher amplitude electrical energythan is used for neuroplasticity reducing electrical stimulation. Inthis case, the neuroplasticity reducing electrical stimulation may bebelow the therapeutic target threshold stimulation (i.e. below thethreshold where therapeutic electrical stimulation is provided to adjustthe level of activity in the target nerve tissue in the person's brainto treat the condition in the person's body). Alternatively,neuroplasticity reducing electrical stimulation may be provided usingthe same or a higher amplitude electrical energy than is used fortherapeutic electrical stimulation (i.e. at or above the threshold wheretherapeutic electrical stimulation is provided to adjust the level ofactivity in the target nerve tissue in the person's brain to treat thecondition in the person's body). In this case, the neuroplasticityreducing electrical stimulation's primary purpose is not to produce atherapeutic effect, but rather to reduce neuroplasticity. In thismanner, the neuroplasticity reducing electrical stimulation could haveboth a therapeutic and neuroplasticity reducing effect.

FIG. 7 illustrates a number of example stimulation programs 156, eachincluding a number of stimulation sets 150. One or more simulationprograms 156 may be set up to reduce neuroplasticity effects associatedwith therapeutic electrical stimulation of the brain. As describedabove, each stimulation set 150 specifies a number of stimulationparameters for the stimulation set 150. In one embodiment, within eachstimulation program 156, stimulation system 10 consecutively executesthe sequence of one or more stimulation sets 150 associated withstimulation program 156. The sequence may be executed only once,repeated a specified number of times, or repeated an unspecified numberof times within a specified time period. For example, as is illustratedin FIG. 8 for the third example stimulation program 156 c includingeight stimulation sets 150, each of the eight stimulation sets 150 isconsecutively executed in sequence. Although the time intervals 158(t1-t0, t2-t1, etc.) during which the stimulation sets 150 are executedare shown as being equal, the present invention contemplates aparticular stimulation set 150 being executed over a different timeinterval 158 than one or more other stimulation sets 150 according toparticular needs. One or more stimulation sets 150 within at least onestimulation program 156 may be set up to provide reduced neuroplasticityeffects associated with therapeutic electrical stimulation of the brain.

Although stimulation system 10 is illustrated by way of example asaccommodating up to twenty-four stimulation programs 156 each includingup to eight stimulation sets 150, the present invention contemplates anyappropriate number of stimulation programs 156 each including anyappropriate number of stimulation sets 150. For example, in a verysimple case, a single stimulation program 156 may include a singlestimulation set 150, whereas in a very complex case more thantwenty-four stimulation programs 156 may each include more than eightstimulation sets 150.

In one embodiment, stimulation system 10 executes only a singlestimulation program 156 in response to user selection of thatstimulation program for execution. In another embodiment, during astimulation period, stimulation system 10 executes a sequence ofpre-programmed stimulation programs 156 for each lead 14 until thestimulation period ends. Depending on the length of the stimulationperiod and the time required to execute a sequence of stimulationprograms 156, the sequence may be executed one or more times. Forexample, the stimulation period may be defined in terms of apredetermined number of cycles each involving a single execution of thesequence of stimulation programs 156, the sequence of stimulationprograms 156 being executed until the predetermined number of cycles hasbeen completed. As another example, the stimulation period may bedefined in terms of time, the sequence of. stimulation programs 156being executed until a predetermined time interval has elapsed or thepatient or another user manually ends the stimulation period. Although asequence of stimulation programs 156 is described, the present inventioncontemplates a single stimulation program being executed one or moretimes during a stimulation period according to particular needs.Furthermore, the present invention contemplates each stimulation program156 being executed substantially immediately after execution of aprevious stimulation program 156 or being executed after a suitable timeinterval has elapsed since completion of the previous stimulationprogram 156. Where stimulation system 10 includes multiple leads 14,stimulation programs 156 for a particular lead 14 may be executedsubstantially simultaneously as stimulation programs 156 for one or moreother leads 14, may be alternated with stimulation programs 156 for oneor more other leads 14, or may be arranged in any other suitable mannerwith respect to stimulation programs 156 for one or more other leads 14.

Where stimulation system 10 provides, in addition to therapeuticelectrical stimulation, electrical stimulation to reduce neuroplasticityeffects, each stimulation program 156 may be particular to either thetherapeutic electrical stimulation or the neuroplasticity reducingelectrical stimulation. For example, one or more stimulation programs156 may be designed to provide therapeutic electrical stimulation andone or more other stimulation programs 156 may be designed to reduceneuroplasticity effects. In this case, the therapeutic stimulationprograms 156 and the neuroplasticity reducing stimulation programs 156may be arranged temporally in any manner. A therapeutic stimulationprogram 156 may be separated from a successive therapeutic stimulationprogram 156 by any number of neuroplasticity reducing stimulationprograms 156 and this number may be the same between each pair oftherapeutic stimulation programs 156 or may vary between each pair oftherapeutic stimulation programs 156 in a predetermined or randomizedmanner. As another example, one or more stimulation programs 156 may beset up to concurrently provide both therapeutic and neuroplasticityreducing electrical stimulation.

In general, each stimulation program 156 may, but need not necessarily,be set up for electrical stimulation of different target nerve tissue ina person's brain. As an example, where therapeutic electricalstimulation of target nerve tissue in a particular region 38 of thebrain is desired, one or more stimulation programs 156 may be set up fortherapeutic electrical stimulation of the target nerve tissue in theparticular region 38 and one or more other stimulation programs 156 maybe set up for electrical stimulation of the same target nerve tissue inthe particular region 38 to reduce neuroplasticity effects associatedwith the therapeutic electrical stimulation. As another example, one ormore stimulation programs 156 may be set up for therapeutic electricalstimulation of target nerve tissue in a particular region 38 of thebrain and one or more other stimulation programs 156 may be set up forelectrical stimulation of different nerve tissue in either the sameregion 38 or in a different region 38 of the brain to reduceneuroplasticity effects associated with the therapeutic electricalstimulation.

As described above, in one embodiment, the nature of any neuroplasticityreducing electrical stimulation may be varied more or less continually,whether in a predetermined or randomized manner, to reduce, prevent,delay, enhance, promote, or otherwise control the ability of the brainto adapt to the neuroplasticity reducing electrical stimulation anddynamically reorganize itself accordingly. In a more particularembodiment, where the neuroplasticity reducing electrical stimulation isprovided concurrently with therapeutic electrical stimulation, theneuroplasticity reducing electrical stimulation may be randomized orotherwise varied about the therapeutic electrical stimulation to achievethis result. In essence, the randomized or otherwise variedneuroplasticity reducing electrical stimulation makes it more difficultfor the brain to dynamically reorganize itself to overcome the effectsof the therapeutic electrical stimulation.

The present invention contemplates any suitable circuitry withinstimulation source 12 for generating and transmitting electricalstimulation pulses for electrically stimulating target nerve tissue in aperson's brain to treat a condition in the person's body and, whereappropriate, to reduce, enhance, or otherwise treat neuroplasticityeffects in the person's brain, whether separate from or concurrentlywith the therapeutic electrical stimulation. Example circuitry that maybe used is illustrated and described in U.S. Pat. No. 6,609,031 B1,which is hereby incorporated by reference herein as if fully illustratedand described herein.

VI. Examples

The following examples are included to demonstrate preferred embodimentsof the invention. It should be appreciated by those of skill in the artthat the techniques disclosed in the examples which follow representtechniques discovered by the inventor to function well in the practiceof the invention, and thus can be considered to constitute preferredmodes for its practice. However, those of skill in the art should, inlight of the present disclosure, appreciate that many changes can bemade in the specific embodiments which are disclosed and still obtain alike or similar result without departing from the spirit and scope ofthe invention.

Example 1 Treatment of Deafferentation Pain

In general, patients with intractable deafferentation pain were selectedfor neuronavigated transcranial magnetic stimulation (TMS) of thesomatosensory cortex.

Prior to TMS a fMRI of the somatosensory cortex was performeddemonstrating the area of reorganization. A fMRI was performed, applyingtactile stimulation at the deafferented area, inducinghyperalgesia/allodynia. The FMRI demonstrated an area of hyperactivityon the contralateral primary/secondary somatosensory cortex.

TMS was used to verify the potential benefit of electrical stimulationof the somatosensory cortex. Subsequently a TMS was performed by meansof fMRI based neuronavigation (Treon, Medtronic) at 90% motor threshold(MT). If pain suppression was obtained, placebo stimulation at the samesite was performed. Stimulation at 110% MT was also tested to excludemotor cortex involvement. The pain suppression obtained by TMS wastransient.

Five of the 8 patients had beneficial effect with TMS and underwent animplantation of a cortical electrode on the somatosensory cortex.Continuous pain suppression was obtained by implantation of an epiduralelectrode (Lamitrode 44, ANS Inc. Plano, Tex.) on the area of corticalreorganization as located by fMRI based neuronavigation. In 3 of 5patients this treatment was highly beneficial, in 1 partly successfuldue to multiple recurrences, requiring reprogrammation, in 1 pain recursafter initial suppression.

Four out of five patients remained pain free without paresthesiasinduced by the cortical stimulation. In one of these patients multiplereprogrammations were required for continuing pain suppression.Initially 4-7 Hz stimulation was used at low amplitudes (0.5-2 mA).Stimulation at higher frequencies and amplitudes induced pain in thearea of deafferentation. In one patients pain recurred after initialsuppression.

Thus, stimulation of the somatosensory cortex stimulation can be usedfor pain control in patients presenting with intractable deafferentationpain.

Example 2 Treatment of Pain Patient History

A 53 year old woman presented with a 10 year history of persistentlancinating pain in the right supraorbital region. The pain arose a fewweeks after a surgical excision of basocellular carcinoma on the rightforehead. Initially she suffered a normal post operative painprogressively evolving to a constant, sharp lancinating pain. Multiplesurgical procedures followed with aggravation of the symptoms.

Except for the pain she also developed a sensation of her right eyebeing located on her right maxillary arc. Despite a normal vision asdemonstrated by an extensive neuro-ophthalmological work-up, the phantomsensation often induced a misperception of the position of surroundingobjects causing her to run into obstacles ipsilateral to the phantomsensation.

Clinical Examination

A hyperalgesia and a loss of sensation of temperature and vibration inthe right VI dermatoma were noted. Tactile stimulation of the medialcornea and upper eyelashes of the right eye were sensed at the phantomeye at the right maxillary arc. Tactile stimulation of the medial corneaand medial upper and lower eyelashes of the phantom eye were sensed atthe corresponding areas at the ipsilateral eye. Phantom corneal reflexwas not elicited. Further clinical exams were normal.

Functional Magnetic Resonance Imaging (fMRI)

fMRI was performed on a 3T MR system using the blood oxygen leveldependend (BOLD) method and consisted of acquisition of whole brainFFE-EPI images (resolution of 3.times.3.times.4 mm, TE/TR=33/3000 ms) aswell as high resolution T1 weighted anatomical images. The stimulationparadigm was a blocked fMRI design alternating 30 s epochs of sensorystimulation (the patient rubbed the painful right V1 skin area using herleft hand) with 30 s epochs of non-stimulation (rest). Statisticalcomparison of brain activity during skin stimulation to rest resulted ina significant area of activity in the left postcentral gyruscorresponding to the area of perception of pain located within the leftprimary sensory cortex (FIG. 9). Other areas of activity were found inleft primary sensorimotor cortex, supplementary motor area, rightcerebellum, and were related to the motor activity of the left hand andarm rubbing the right VI skin area.

Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation was performed with a Super Rapidmagnetic stimulator (Magstim Inc, Wales, UK.) allowing stimulation in arange of 1 to 50 Hz. Magnetic stimulation was performed afterneuronavigation guided localization (Stealth, Sofamor Danek, Colo., USA)of the area of cortical reorganization based on the predefined area onthe FMRI. Several series of stimulation were applied with differentfrequencies and intensities on target and adjacent areas.

The transcranial magnetic stimulation (TMS) caused a maximum reductionof 80% of the supraorbital pain and a complete disappearance of thephantom sensation.

The suppression of the pain was obtained immediately after starting theTMS and had a residual effect whereas the phantom shifted back to itsnormal position after a longer period of stimulation.

TMS on target (FIG. 9) using a rate of 1 pulse per second (pps) during60 seconds at an intensity of 90% motor threshold (MT) caused animmediate pain reduction of 80% and complete disappearance of thephantom sensation after 25 seconds of stimulation. The same pain reliefwas obtained with TMS at a rate of 5 pps and 90% MT but the phantom eyeshifted back in 10 seconds. TMS with 10 consecutive 500 ms bursts at 20pps at 90% MT had no beneficial effect on the pain or the phantom.Lowering the output to 80% MT at a rate of 1 pps still induced an 80%pain reduction but the phantom progressively disappeared after 35seconds of stimulation. Sham stimulation had no effect. TMS at 110% MTdid not elicit any motor activity. (FIG. 10)

Consecutively an epidural octopolar electrode (Lamitrode 44, AdvancedNeuromodulation Systems Inc, Tx, USA.) was implanted for electricalstimulation of the somatosensory cortex. The electrode was located atthe predefined target using FMRI based frameless stereotaxic guidance.The leads of the electrodes were tunneled subcutaneously to theabdominal wall and connected to the internal pulse generator (IPG)(Genesis, Advanced Neuromodulation Systems Inc. Tx, USA) and implantedin a subcutaneous pocket. The postoperative course was uneventful.

After recovery from the surgery the patient felt the same pain andphantom sensation as preoperatively. On the first postoperative day theIPG was activated and a complete suppression of pain and a completedisappearance of the phantom eye was obtained. Stimulation parameterswere set in an alternating 30 seconds ON and 60 seconds OFF mode with50.mu.sec pulse width, 4 pps at 1.0 mA. Stimulating with theseparameters induced paresthesias in the right supraorbital region.Lowering the intensity to 0.3 mA had a similar effect on the pain andphantom but without any paresthesias. Furthermore the patient had noproblem in determining the exact position of surrounding objects afterstimulation parameters were set.

Patient was discharged 4 days after surgery completely free of pain andphantom sensation and remained as such after 12 months follow-up.

Postoperative images revealed a correct position of the lead on thesomatosensory cortex and not on the motor cortex (FIGS. 11A and B).Thus, somatosensory cortex stimulation can be used for anaesthesiadolorosa and phantom sensation.

REFERENCES CITED

All patents and publications mentioned in the specifications areindicative of the levels of those skilled in the art to which theinvention pertains. All patents and publications are herein incorporatedby reference to the same extent as if each individual publication wasspecifically and individually indicated to be incorporated by reference.

-   Brown J A, Barbaro N M. Motor cortex stimulation for central and    neuropathic pain: current status. Pain 2003 August; 104 (3): 431-435-   Bruehlmeier M, Dietz V, Leenders K L, Roelcke U, Missimer J, Curt A.    How does the human brain deal with a spinal cord injury? Eur J    Neurosci. 1998 December; 10(12): 3918-22-   Condes-Lara M, Barrios F A, Romo J R, Rojas R, Salgado P,    Sanchez-Cortazar J. Brain somatic representation of phantom and    intact limb: a FMRI study case report. Eur J Pain. 2000;    4(3):239-45.-   De Ridder D, De Mulder G, Walsh V, Muggleton N, Sunaert S, Moller A.    Magnetic and electrical stimulation of the auditory cortex for    intractable tinnitus. Case report. J Neurosurg 2004 March; 100(3):    560-564-   Doetsch G S, Harisson T A, MacDonald A C, Litaker M S. Short term    plasticity in primary somatosensory cortex of the rat: rapid changes    in magnitudes and latencies of neuronal responses following digit    denervation. Exp Brain Res 1996 December; 112: 505-512-   Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N,    Larbig W, Taub E. Phantom limb pain as a perceptual correlate of    cortical reorganization following arm amputation. Nature 1995 June;    8: 375 (6531): 482-484-   Flor H. Cortical reorganization and chronic pain: implications for    rehabilitation. J Rehabil Med. 2003 May; 41 Suppl: 66-72-   Halbert J, Crotty M, Cameron I D. Evidence for the optimal    management of acute and chronic phantom pain: a systematic review.    Clin J Pain. 2002 March-April; 18(2): 84-92-   Jastreboff P J. Phantom auditory perception (tinnitus): Mechanisms    of generation and perception. Neurosci Res. 1990 August; 8(4):    221-254-   Kaas J H, Merzenich M M, Killackey H P. The reorganization of    somatosensory cortex following peripheral nerve damage in adult and    developing mammals. Annu Rev Neurosci. 1983; 6: 325-56-   Katayama Y, Yamamoto T, Kobayashi K, Kasai M, Oshima H, Fukaya C.    Motor cortex stimulation for phantom limb pain: comprehensive    therapy with spinal cord and thalamic stimulation. Stereotact Funct    Neurosurg. 2001; 77(1-4): 159-62-   Kandel E R. Cellular mechanisms of hearing and the biological basis    of individuality. Principles of Neural Science, 3rd ed, Appleton &    Lange Norwalk, Conn.: 1009-1031, 1991-   Knecht S, Henningsen H, Hohling C, Elbert T, Flor H, Pantev C.    Plasticity of plasticity? Changes in the pattern of perceptual    correlates of reorganization after amputation. Brain 1998 April;    121(Pt4): 717-724-   Kumar K, Toth C, Nath R K. Deep brain stimulation for intractable    pain: a 15 year experience. Neurosurgery 1997 April; 40(4):736-746-   Lende R, Kirsch W, Druckman R. Relief of facial pain after combined    removal of precentral and postcentral cortex. J Neurosurg 1971; 34:    537-543-   Lenz F, Kwan H, Dostrovsky J O, Tasker R R. Characteristics of the    bursting pattern of action potentials that occurs in the thalamus of    patients with central pain. Brain Res. 1989 September; 496 (1-2):    357-360-   Levy R M, Lamb S, Adams J E. Treatment of chronic pain by deep brain    stimulation: long term follow-up and review of the literature.    Neurosurgery 1987 December; 21(6): 885-893-   Lotze M, Flor H, Grodd W, Larbig W, Birbaumer N. Phantom movements    and pain. An f MRI study in upper limb amputees. Brain 2001    November; 124 (Pt11): 2268-2277-   Merzenich M M, Nelson R J, Stryker M P, Cynader M S, Schoppmann A,    Zook J M. Somatosensory cortical map changes following digit    amputation in adult monkeys. J Comp Neurol. 1984 Apr. 20;    224(4):591-605.-   Moller A R. Similarities between chronic pain and tinnitus. AM J    Otol. 1997 September; 18: 577-585-   Moller A R: The role of neural plasticity in disorders of the    nervous system. Cambridge University Press, In press-   Nguyen J P, Keravel Y, Feve A, Uchiyama T, Cesaro P, Le Guerinel C,    Pollin B. Treatment of deafferentation pain by chronic stimulation    of the motor cortex. Report of a series of 20 cases. Acta Neurochir    Suppl (Wien) 1997; 68: 54-60-   Nikolajsen L, Jensen T S. Phantom limb pain. Br J Anaesth. 2001    July; 87(1): 107-16-   Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain    responses to pain. A review and meta-analysis (2000). Neurophysiol    Clin. 2000 October; 30(5): 263-88-   Pons T P, Garraghty P E, Ommaya A K, Kaas J H, Taub E, Mishkin M.    Massive cortical reorganization after sensory deafferentation in    adult macaques. Science. 1991 Jun. 28; 252 (5014): 1857-1860-   Ramachandran V S. Behavioral and magnetoencephalographic correlates    of plasticity in the adult human brain. Proc. Natl. Acad. Sci. USA.    1993 Nov. 15; 90(22): 10413-20-   Ramachandran V S, Hirstein W. The perception of phantom limbs.    The D. O. Hebb lecture. Brain 1998 September 121(Pt9): 1603-1630-   Rinaldi P C, Young R F, Albe-Fessard D, Chodakiewitz J. Spontaneous    neuronal hyperactivity in the medial and intrlaminar thalamic nuclei    of patients with deafferentation pain. J Neurosurg 1991 March; 74:    415-421-   Sherman R A, Sherman C J, Parker L. Chronic phantom and stump pain    among American veterans: results of a survey. Pain 1984 January;    18(1): 83-95-   Theuvenet P J, Dunajski Z, Peters M J, Van Ree J M. Responses to    median and tibial nerve stimulation in patients with chronic    neuropathic pain. Brain Topogr 1999 Summer; 11 (4): 305-313-   Tonndorf J. The analogy between tinnitus and pain: a suggestion for    a physiological basis of chronic tinnitus. Hear Res 1987; 28 (2-3):    271-275-   Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S. Chronic    motor cortex stimulation for the treatment of central pain. Acta    Neurochir Suppl (Wien) 1991; 52: 137-139-   Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S. Treatment    of thalamic pain by chronic motor cortex stimulation. Pacing Clin    Electrophysiol 1991 January 14(1): 131-124-   Weiss T, Miltner W H, Huonker R, Friedel R, Schmidt I, Taub E. Rapid    functional plasticity of the somatosensory cortex after finger    amputation. Exp Brain Res. 2000 September; 134(2): 199-203-   Wiech K, Preissl H, Lutzenberges W, Kiefer R T, Topfner S, Haerle M,    Schaller H G, Birbaumer N. Cortical reorganization after digit to    hand replantation. J. Neurosurg 2000 November; 93(5): 876-883-   Yuste R, Sur M. Development and plasticity of the cerebral cortex:    from molecules to maps. J. Neurobiol 1999 October; 41(1): 1-6

Although the present invention and its advantages have been described indetail, it should be understood that various changes, substitutions andalterations can be made herein without departing from the spirit andscope of the invention as defined by the appended claims. Moreover, thescope of the present application is not intended to be limited to theparticular embodiments of the process, machine, manufacture, compositionof matter, means, methods and steps described in the specification. Asone of ordinary skill in the art will readily appreciate from thedisclosure of the present invention, processes, machines, manufacture,compositions of matter, means, methods, or steps, presently existing orlater to be developed that perform substantially the same function orachieve substantially the same result as the corresponding embodimentsdescribed herein may be utilized according to the present invention.Accordingly, the appended claims are intended to include within theirscope such processes, machines, manufacture, compositions of matter,means, methods, or steps.

What is claimed:
 1. A method of treating a neurological condition in asubject comprising the steps of: determining a target site of in a brainof the subject to be stimulated, wherein said determining comprisesmapping the brain to identify an area of the brain having alteredneuronal activity, said identified area is the target site; placing anelectrode in communication with the target site; and providing astimulation signal to the electrode to stimulate the target site totreat the neurological condition.
 2. The method of claim 1, wherein theneurological condition is selected from the group consisting of pain,tinnitus, depression, phantom perception, pareshesias, synesthesia,hyperalgesia, allodynia, dysesthesias, dyskinesia, tremor, dystonia,chorea and ballism, tic syndromes, Tourette's Syndrome, myoclonus,drug-induced movement disorders, Wilson's Disease, ParoxysmalDyskinesias, Stiff Man Syndrome and Akinetic-Ridgid Syndromes andParkinsonism.
 3. The method of claim 1, wherein the altered neuronalactivity is an increase in neuronal activity.
 4. The method of claim 1,wherein the altered neuronal activity is a decrease in neuronalactivity.
 5. The method of claim 1, wherein the identified area islocated in the cortex.
 6. The method of claim 1, wherein the identifiedarea is located in the somatosensory cortex.
 7. The method of claim 1,wherein the identified area is located in a cortical or cerebellar areaof reorganization.
 8. The method of claim 1, wherein the neurologicalcondition is acute pain, subacute pain or chronic pain.
 9. The method ofclaim 2, wherein the mapping is neurophysiological mapping.
 10. Themethod of claim 2, wherein the mapping is performed by the techniquesselected from the group consisting of positron emission tomography(PET), magnetic resonance imaging (MRI), functional MRI (fMRI),electroencephalography (EEG), magnetoencephalography (MEG), x-raycomputed tomography (CT), single photon emission computed tomography(SPECT), brain electrical activity mapping (BEAM), transcranial magneticstimulation (TMS), electrical impedance tomography (EIT), near-infraredspectroscopy (NIRS) and optical imaging.
 11. An electrical stimulationsystem for electrically stimulating a target tissue in a brain of asubject to treat a neurological condition, comprising: an electrode forelectrical stimulation of the target tissue; a pulse generating sourceoperable to generate electrical stimulation pulses for transmission tothe electrodes to cause the electrodes to deliver electrical stimulationpulses to the target tissue to treat neuroplasticity effects in thesubject's brain while delivering electrical stimulation pulses fortreating the neurological condition.
 12. The system of claim 12, whereinthe target tissue is identified using brain mapping to determine a siteof altered neuronal activity.
 13. The system of claim 12, wherein theelectrode is positioned in communication with the target tissue.
 14. Thesystem of claim 12, wherein the pulse generating source is operable togenerate the electrical stimulation pulses according to one or morestimulation sets each specifying a plurality of stimulation parameters,the stimulation parameters for a stimulation set comprising a polarityfor each electrode at each of one or more times within a stimulationpulse for the stimulation set.
 15. The system of claim 12, whereintreating neuroplasticity effects in the person's brain comprisesreducing neuroplasticity effects in the person's brain.
 16. The systemof claim 12, wherein treating neuroplasticity effects in the person'sbrain comprises enhancing neuroplasticity effects in the person's brain.17. The system of claim 12, wherein the electrode is a percutaneous leador laminotomy lead.